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结直肠癌干细胞研究历程2007至今 [复制链接]

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发表于 2012-3-6 21:51 |只看该作者 |倒序浏览 |打印
主要收集了2007至今结直肠癌干细胞研究的文献和综述,与大家分享。% Z1 h' U& V! ~6 ]4 M) q6 H

% N9 P- t! y( S$ A  }$ q8 ^1 P. t1 J【1】 2006年底nature同期发布两篇关于结直肠癌干细胞的论文
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+ l# H& @  ^' j% n. ]Nature. 2007 Jan 4;445(7123):106-10. Epub 2006 Nov 19.! Q1 b2 u* _6 }% Y. k
A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.* ?$ q: T- X2 ]& u. t$ u
O'Brien CA, Pollett A, Gallinger S, Dick JE.
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Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
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Abstract8 q2 W4 f# m' W/ K4 f; [
Colon cancer is one of the best-understood neoplasms from a genetic perspective, yet it remains the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. What has yet to be established is whether every colon cancer cell possesses the potential to initiate and sustain tumour growth, or whether the tumour is hierarchically organized so that only a subset of cells--cancer stem cells--possess such potential. Here we use renal capsule transplantation in immunodeficient NOD/SCID mice to identify a human colon cancer-initiating cell (CC-IC). Purification experiments established that all CC-ICs were CD133+; the CD133- cells that comprised the majority of the tumour were unable to initiate tumour growth. We calculated by limiting dilution analysis that there was one CC-IC in 5.7 x 10(4) unfractionated tumour cells, whereas there was one CC-IC in 262 CD133+ cells, representing >200-fold enrichment. CC-ICs within the CD133+ population were able to maintain themselves as well as differentiate and re-establish tumour heterogeneity upon serial transplantation. The identification of colon cancer stem cells that are distinct from the bulk tumour cells provides strong support for the hierarchical organization of human colon cancer, and their existence suggests that for therapeutic strategies to be effective, they must target the cancer stem cells.9 B$ A) A$ p' @: l- V$ l1 [# O
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Nature. 2007 Jan 4;445(7123):111-5. Epub 2006 Nov 19.
! U$ g( ]2 Z2 U$ ~7 DIdentification and expansion of human colon-cancer-initiating cells.
. }! v. D: ]% i& yRicci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R.
9 M) v  p. m/ M$ v. y- ?1 KSource/ w% q* c8 s! C/ X* \: j
Department of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.0 [9 t  n+ J. r) F, ~; s
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Abstract: y) `: o0 ?5 T& p- T" H
Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.
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【2】2007年PNAS发布了CSC大牛Clarke MF关于结直肠癌干细胞的论文
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% n! U& G: M. a9 M, E3 O4 xProc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63. Epub 2007 Jun 4.* B) J) O' B# X/ X+ i0 H
Phenotypic characterization of human colorectal cancer stem cells.( K* k% v6 x, g4 O: c
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF.1 l2 I- l% w7 r) [" d
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Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.) u: q3 o# F7 m% t

1 C1 M: C- O5 ^4 o/ ?2 zAbstract; a) T- u, K: ?" s  V
Recent observations indicate that, in several types of human cancer, only a phenotypic subset of cancer cells within each tumor is capable of initiating tumor growth. This functional subset of cancer cells is operationally defined as the "cancer stem cell" (CSC) subset. Here we developed a CSC model for the study of human colorectal cancer (CRC). Solid CRC tissues, either primary tissues collected from surgical specimens or xenografts established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into single-cell suspensions and analyzed by flow cytometry. Surface markers that displayed intratumor heterogeneous expression among epithelial cancer cells were selected for cell sorting and tumorigenicity experiments. Individual phenotypic cancer cell subsets were purified, and their tumor-initiating properties were investigated by injection in NOD/SCID mice. Our observations indicate that, in six of six human CRC tested, the ability to engraft in vivo in immunodeficient mice was restricted to a minority subpopulation of epithelial cell adhesion molecule (EpCAM)(high)/CD44+ epithelial cells. Tumors originated from EpCAM(high)/CD44+ cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Analysis of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the identification of CD166 as an additional differentially expressed marker, useful for CSC isolation in three of three CRC tested. These results validate the stem cell working model in human CRC and provide a highly robust surface marker profile for CRC stem cell isolation.
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7 b( Y6 d8 Y# G9 Y: m【3】2007年 cell stem cell 再发结直肠癌干细胞论文5 t- f2 ?, l; k1 m
Cell Stem Cell. 2007 Oct 11;1(4):389-402.9 p/ R3 I* _/ ^* E* r" o# ]7 a: d2 B
Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4.
! Q5 c& s2 N+ Q1 STodaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G.% ]0 |9 B* l2 y  M' T
Source
5 }" A4 V" n1 M( x6 q2 BDepartment of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, 90127 Palermo, Italy.
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Abstract
; V9 n0 X8 E8 L6 @( Z7 ^  SA novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, treatment with IL-4Ralpha antagonist or anti-IL-4 neutralizing antibody strongly enhances the antitumor efficacy of standard chemotherapeutic drugs through selective sensitization of CD133(+) cells. Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4.
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【4】2008年JCI发布一篇论文对CD133作为结肠癌干细胞标记物提出质疑。5 y' T0 j/ K# ~# J, Y3 W
J Clin Invest. 2008 Jun;118(6):2111-20.
) c3 h0 T6 B* L/ K3 OCD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors./ z, [% W( A# b4 w9 J' J/ ~; h! w
Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, St Clair R, Baljevic M, White I, Jin DK, Chadburn A, Murphy AJ, Valenzuela DM, Gale NW, Thurston G, Yancopoulos GD, D'Angelica M, Kemeny N, Lyden D, Rafii S.
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# g6 z, s. ]% b7 \( tHoward Hughes Medical Institute, Ansary Center for Stem Cell Therapeutics, and Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York, USA.) l- l2 p0 i: G# \8 p( ^
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Abstract
* \! f7 M6 n% L* v& X6 aColon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10-/-CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133- population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133- metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133- cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24-), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133+ tumor cells might give rise to the more aggressive CD133(- )subset, which is also capable of tumor initiation in NOD/SCID mice.
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【5】2008年年底nature再次同期发布两篇结直肠癌干细胞论文/ |# j& S# z; f. f. |* f
Nature. 2009 Jan 29;457(7229):608-11. Epub 2008 Dec 17., Y9 D. o' ?% Q$ Z# |& v" _3 @( C
Crypt stem cells as the cells-of-origin of intestinal cancer.
* Y  B% D( G" V3 n; fBarker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H(胃肠道肿瘤干细胞大牛).3 C0 @9 L& E1 {% ~; K* t' b1 s3 k
Source
5 J  u8 h& f$ ]; X) x/ m3 g- U4 ?Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584CT Utrecht & University Medical Centre Utrecht, Netherlands.& e' h2 E. Z) r) @
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Abstract! H# X* |) Z# z$ ?4 q7 w: D
Intestinal cancer is initiated by Wnt-pathway-activating mutations in genes such as adenomatous polyposis coli (APC). As in most cancers, the cell of origin has remained elusive. In a previously established Lgr5 (leucine-rich-repeat containing G-protein-coupled receptor 5) knockin mouse model, a tamoxifen-inducible Cre recombinase is expressed in long-lived intestinal stem cells. Here we show that deletion of Apc in these stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fuelling a growing microadenoma. These microadenomas show unimpeded growth and develop into macroscopic adenomas within 3-5weeks. The distribution of Lgr5(+) cells within stem-cell-derived adenomas indicates that a stem cell/progenitor cell hierarchy is maintained in early neoplastic lesions. When Apc is deleted in short-lived transit-amplifying cells using a different cre mouse, the growth of the induced microadenomas rapidly stalls. Even after 30weeks, large adenomas are very rare in these mice. We conclude that stem-cell-specific loss of Apc results in progressively growing neoplasia.
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1 g( x1 ?7 e+ x3 DNature. 2009 Jan 29;457(7229):603-7. Epub 2008 Dec 17.! w/ J4 N- s6 k& Y% y
Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation.
; m2 K- ^, |0 B! O) \, n- qZhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ.
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8 E" H8 T$ R1 N; r" {; [% A" ODepartment of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA." \1 F6 a3 O+ v0 \: P) o$ u& t; @

! Z( t4 D  i& }% }6 ^Abstract/ m9 a. h+ H+ m+ g5 Z, s/ s0 H
Cancer stem cells are remarkably similar to normal stem cells: both self-renew, are multipotent and express common surface markers, for example, prominin 1 (PROM1, also called CD133). What remains unclear is whether cancer stem cells are the direct progeny of mutated stem cells or more mature cells that reacquire stem cell properties during tumour formation. Answering this question will require knowledge of whether normal stem cells are susceptible to cancer-causing mutations; however, this has proved difficult to test because the identity of most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear LacZ reporter allele knocked into the Prom1 locus (Prom1(C-L)), we show that Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing studies of adult Prom1(+/C-L) mice containing the Rosa26-YFP reporter allele showed that Prom1(+) cells are located at the base of crypts in the small intestine, co-express Lgr5 (ref. 2), generate the entire intestinal epithelium, and are therefore the small intestinal stem cell. Prom1 was reported recently to mark cancer stem cells of human intestinal tumours that arise frequently as a consequence of aberrant wingless (Wnt) signalling. Activation of endogenous Wnt signalling in Prom1(+/C-L) mice containing a Cre-dependent mutant allele of beta-catenin (Ctnnb1(lox(ex3))) resulted in a gross disruption of crypt architecture and a disproportionate expansion of Prom1(+) cells at the crypt base. Lineage tracing demonstrated that the progeny of these cells replaced the mucosa of the entire small intestine with neoplastic tissue that was characterized by focal high-grade intraepithelial neoplasia and crypt adenoma formation. Although all neoplastic cells arose from Prom1(+) cells in these mice, only 7% of tumour cells retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells.
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& P4 y3 g3 k/ Q【6】2008年cancer research和PNAS上的论文,从不同角度研究结直肠癌干细胞。
0 Q+ s) E) s( m+ X5 U) {Cancer Res. 2008 Sep 1;68(17):6932-41.
9 X+ q0 A& h" }. T" v( x! }% vA stochastic model for cancer stem cell origin in metastatic colon cancer.* A% \( _7 T: A4 _& B* C
Odoux C, Fohrer H, Hoppo T, Guzik L, Stolz DB, Lewis DW, Gollin SM, Gamblin TC, Geller DA, Lagasse E.
- X+ b; r! p/ X& bSource+ @8 R2 t' A. n  r0 p
McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh Medical School, 100 Technology Drive, Suite 200, Pittsburgh PA, 15219-3130, USA.
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Abstract
, o6 H0 Z& ^, x% t8 S! w5 \Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.
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+ O, P+ N1 f! A1 I3 t8 [, NProc Natl Acad Sci U S A. 2008 Sep 9;105(36):13427-32. Epub 2008 Sep 2.
& D- P1 F) q$ ]- dSingle-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.
* W  Z8 e6 a; z( Y" PVermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, Richel DJ, Stassi G, Medema JP./ ~& G  F0 V/ R+ l+ a, {
Source
3 {! z, y+ ~4 K' V: ~1 X) nLaboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9 1105 AZ, Amsterdam, The Netherlands.
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Abstract) K  k0 u; @, x
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear beta-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.
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发表于 2012-3-6 22:15 |只看该作者
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3 w/ V$ q/ K5 T3 J( }; ~  L1 _8 c【7】2009年cancer research又发布两篇论文。
. v4 \* f5 j/ I% }1 \Cancer Res. 2009 Apr 15;69(8):3382-9. Epub 2009 Mar 31.
5 H0 V- {& Y+ YAldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis.! ~* ]7 \. E" R4 E$ e% U# T* c0 E
Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM.
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Department of Surgery, University of Florida, Gainesville, Florida, USA.
: [: q6 h( Q$ u6 ~Abstract
- g5 S" I% }2 F9 I/ J# PAlthough the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identification and isolation of SC from normal and malignant colon. Accordingly, aldehyde dehydrogenase 1 (ALDH1) was investigated as a possible marker for identifying colonic SC and for tracking them during cancer progression. Immunostaining showed that ALDH1(+) cells are sparse and limited to the normal crypt bottom, where SCs reside. During progression from normal epithelium to mutant (APC) epithelium to adenoma, ALDH1(+) cells increased in number and became distributed farther up the crypt. CD133(+) and CD44(+) cells, which are more numerous and broadly distributed in normal crypts, showed similar changes during tumorigenesis. Flow cytometric isolation of cancer cells based on enzymatic activity of ALDH (Aldefluor assay) and implantation of these cells in nonobese diabetic-severe combined immunodeficient mice (a) generated xenograft tumors (Aldefluor(-) cells did not), (b) generated them after implanting as few as 25 cells, and (c) generated them dose dependently. Further isolation ofcancer cells using a second marker (CD44(+) or CD133(+) serially) only modestly increased enrichment based on tumor-initiating ability. Thus, ALDH1 seems to be a specific marker for identifying, isolating, and tracking human colonic SC during CRC development. These findings also support our original hypothesis, derived previously from mathematical modeling of crypt dynamics, that progressive colonic SC overpopulation occurs duringcolon tumorigenesis and drives CRC development.
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+ E7 o8 K2 o7 ]Cancer Res. 2009 Oct 15;69(20):8208-15. Epub 2009 Oct 6.
2 R/ C( @5 w3 z2 V- C' KAldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in thetransition from colitis to cancer.2 Y1 U7 \3 @3 y+ M0 W& E# P
Carpentino JE, Hynes MJ, Appelman HD, Zheng T, Steindler DA, Scott EW, Huang EH.
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McKnight Brain Institute, University of Florida, Gainesville, Florida 32609, USA.
) K0 h  q( ^- t% c+ c/ P" HAbstract5 A7 W5 Q- I3 {2 D$ n$ y% u9 H
Patients with chronic ulcerative colitis are at increased risk of developing colorectal cancer. Although current hypotheses suggest that sporadic colorectal cancer is due to inability to control cancer stem cells, the cancer stem cell hypothesis has not yet been validated in colitis-associatedcancer. Furthermore, the identification of the colitis to cancer transition is challenging. We recently showed that epithelial cells with the increased expression of aldehyde dehydrogenase in sporadic colon cancer correlate closely with tumor-initiating ability. We sought to determine whether ALDH can be used as a marker to isolate tumor-initiating populations from patients with chronic ulcerative colitis. We used fluorescence-activated cell sorting to identify precursor colon cancer stem cells from colitis patients and report both their transition to cancerous stem cells in xenografting studies as well as their ability to generate spheres in vitro. Similar to sporadic colon cancer, these colitis-derived tumors were capable of propagation as sphere cultures. However, unlike the origins of sporadic colon cancer, the primary colitic tissues did not express any histologic evidence of dysplasia. To elucidate a potential mechanism for our findings, we compared the stroma of these different environments and determined that at least one paracrine factor is up-regulated in the inflammatory and malignant stroma compared with resting, normal stroma. These data link colitis andcancer identifying potential tumor-initiating cells from colitic patients, suggesting that sphere and/or xenograft formation will be useful to survey colitic patients at risk of developing cancer.
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【8】2010年cell stem cell发布了关于转移性结直肠癌干细胞的论文。* [& U: }% Z" ^
Cell Stem Cell. 2010 Jun 4;6(6):603-15.
" g" }% {( n  R8 a3 Z" `  m" gA subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer.! O. N$ Q2 d" L6 Z6 F
Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC.
6 v8 `1 W  x2 H5 y6 @9 e$ lSource
7 p( o' C) I* ?9 Z4 F6 Z+ iDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.
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' H5 j" v5 H0 _3 A" z( mAbstract
8 q! J5 @0 f. J7 S1 SRecent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumor growth in colorectal cancer. However, the role of CSCs in colorectal cancer metastasis is unclear. Here, we identified a subpopulation of CD26(+) cells uniformly present in both the primary and metastatic tumors in colorectal cancer patients with liver metastasis. Furthermore, in patients without distant metastasis at the time of presentation, the presence of CD26(+) cells in their primary tumors predicted distant metastasis on follow-up. Isolated CD26(+) cells, but not CD26(-) cells, led to development of distant metastasis when injected into the mouse cecal wall. CD26(+) cells were also associated with enhanced invasiveness and chemoresistance. Our findings have uncovered a critical role of CSCs in metastatic progression of cancer. Furthermore, the ability to predict metastasis based on analysis of CSC subsets in the primary tumor may have important clinical implication as a selection criterion for adjuvant therapy.5 ~. [# ^4 O: a# v/ x6 R
Copyright 2010 Elsevier Inc. All rights reserved.
' R- E: v( a# Y6 ^" N) S+ ^Comment in
; x/ ]5 E" T1 }Cell Stem Cell. 2010 Jun 4;6(6):502-3.3 Q: l: V# F) N" Z6 x
PMID: 20569697 [PubMed - indexed for MEDLINE]8 v; v) o1 p, ?8 u7 n
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【9】2010年nature cell biology 发布了wnt通路与结肠癌干细胞关系的论文。/ i* ^1 Y9 W* d; Q# P2 P/ l; h% a+ `
Nat Cell Biol. 2010 May;12(5):468-76. Epub 2010 Apr 25.
' C- `+ v: I# uWnt activity defines colon cancer stem cells and is regulated by the microenvironment.
! H% n- ]8 y$ I9 F& m+ O' jVermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP./ ^# p! o9 p4 ^$ [( G
Source
; \$ [: b$ ~* Q" p+ [$ GLaboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.7 Q, z/ b0 B) u4 o  O% E

! @  e* V6 l0 t  n& w9 j8 DAbstract6 a- U$ c' P4 O$ P
Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with a Wnt reporter construct and observed that high Wnt activity functionally designates the colon cancer stem cell (CSC) population. In adenocarcinomas, high activity of the Wnt pathway is observed preferentially in tumour cells located close to stromal myofibroblasts, indicating that Wnt activity and cancer stemness may be regulated by extrinsic cues. In agreement with this notion, myofibroblast-secreted factors, specifically hepatocyte growth factor, activate beta-catenin-dependent transcription and subsequently CSC clonogenicity. More significantly, myofibroblast-secreted factors also restore the CSC phenotype in more differentiated tumour cells both in vitro and in vivo. We therefore propose that stemness of colon cancer cells is in part orchestrated by the microenvironment and is a much more dynamic quality than previously expected that can be defined by high Wnt activity./ o# }" o# H4 }; O8 r! [
Comment in  J/ q  t, u) N- Y; z& X
Nat Cell Biol. 2010 May;12(5):419-21.* O* D: O/ ~9 c4 J) q
Nat Rev Cancer. 2010 Jun;10(6):386.
  N% C- a, [6 ~5 M' KPMID: 20418870 [PubMed - indexed for MEDLINE]' @; ]2 G1 G! F- [& ]4 f% I$ O$ j

+ h7 O9 F9 Y& m. l. N1 J* c+ Z' B【10】2010年PNAS又发结直肠癌细胞株中的癌干细胞论文。4 \6 O' r* u; Q' e# Q
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3722-7. Epub 2010 Feb 2., R, l; u! d% P5 Y( ~
Cancer stem cells from colorectal cancer-derived cell lines.# R4 t' _: x6 s
Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF.4 B& ~9 P% ]5 X  U7 F+ ?
Source
  M) O: i$ e6 d. `Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
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0 s* I3 |; Q" ^5 e8 q  S5 ]Abstract5 \! x% E& a2 X, g
Cancer stem cells (CSCs) are the subpopulation of cells within a tumor that can self-renew, differentiate into multiple lineages, and drive tumor growth. Here we describe a two-pronged approach for the identification and characterization of CSCs from colorectal cancer cell lines, using a Matrigel-based differentiation assay, and cell surface markers CD44 and CD24. About 20 to 30% of cells from the SW1222 cell line form megacolonies in Matrigel that have complex 3D structures resembling colonic crypts. The megacolonies' capacity to self-renew in vitro is direct evidence that they contain the CSCs. Furthermore, just 200 cells from SW1222 megacolonies initiate tumors in NOD/SCID mice. We also showed that CD44(+)CD24(+) cells enriched for colorectal CSCs in the HT29 and SW1222 cell lines, which can self-renew and reform all four CD44/CD24 subpopulations, are the most clonogenic in vitro and can initiate tumors in vivo. A single SW1222 CD44(+)CD24(+) CSC, when grown in Matrigel, can form large megacolonies that differentiate into enterocyte, enteroendocrine, and goblet cell lineages. The HCT116 line does not differentiate or express CDX1, nor does it contain subpopulations of cells with greater tumor-forming capacity, suggesting that HCT116 contains mainly CSCs. However, forced expression of CDX1 in HCT116 leads to reduced clonogenicity and production of differentiating crypt-containing colonies, which can explain the selection for reduced CDX1 expression in many colorectal cancers. In summary, colorectal cancer cell lines contain subpopulations of CSCs, characterized by their cell surface markers and colony morphology, which can self-renew and differentiate into multiple lineages.
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【11】2011年nature medicine发布了正常结肠干细胞的论文。5 q" d4 S% \1 L4 O, U
Nat Med. 2011 Sep 4;17(10):1225-7. doi: 10.1038/nm.2470.
) l9 D% P( E# aIsolation and in vitro expansion of human colonic stem cells.
$ \4 L+ v& d+ j! U2 j& rJung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, Auer H, Gallardo M, Blasco MA, Sancho E, Clevers H, Batlle E.
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Oncology program, Institute for Research in Biomedicine, Barcelona, Spain.7 F& w: `4 V# k1 r# p8 w! f

. K  j4 }) v" y  O3 d0 EAbstract
; v3 z3 M3 I. C1 ~' p# b) @Here we describe the isolation of stem cells of the human colonic epithelium. Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows the purification of different cell types from human colon mucosa biopsies. The highest EPHB2 surface levels correspond to epithelial colonic cells with the longest telomeres and elevated expression of intestinal stem cell (ISC) marker genes. Moreover, using culturing conditions that recreate the ISC niche, a substantial proportion of EPHB2-high cells can be expanded in vitro as an undifferentiated and multipotent population.. F( g# w* q. l2 `* ^
PMID: 21892181 [PubMed - indexed for MEDLINE]

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发表于 2012-3-6 22:31 |只看该作者
回复 csc1981 的帖子
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除了这几篇重量级的论文外还有很多有价值的论文,与大家一起分享。. T7 Z6 F) E: s% m0 U+ Z& _/ I* l
不足之处,大家补充啊。
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( U# p! v8 P" _( z; m$ V6 HDalerba, P        2007        Phenotypic characterization of human colorectal cancer stem cells.
7 e7 j9 v# Y7 P" h, x5 ~7 Z' hProc Natl Acad Sci U S A2 d4 K3 Z7 |3 q3 N$ ]2 E: k
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' S, O) g* W& i- F1 }# d$ J- S% TO'Brien, CA        2007        A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.
3 F/ {& b! U; [  t: CNature
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8 e* a4 z9 w% B) K3 ?2 ]& A! M6 t# yRicci-Vitiani, L        2007        Identification and expansion of human colon-cancer-initiating cells.* k4 p! L  ?( A) D9 k4 o) _4 n
Nature1 R. ]1 F9 _7 f) X# ^9 L
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Schulenburg, A        2007        CD44-positive colorectal adenoma cells express the potential stem cell markers musashi antigen (msi1) and ephrin B2 receptor (EphB2).
& ]& }: F5 i: v" x; O5 JJ Pathol& c- m" a9 D* m5 J
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" I* A# e+ y( V5 s% T* P1 @1 E5 L1 zTodaro, M        2007        Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4.
! H# ^$ r  O( a3 _' q% c9 bCell Stem Cell
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6 {* E2 Q" T6 B, l8 ?; [% K) lBarker, N        2008        Crypt stem cells as the cells-of-origin of intestinal cancer.# Q% \% v: U8 A. Q; `  T( d; H( D0 d2 ]
Nature
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Barker, N        2008        The intestinal stem cell.
" W: B6 i2 d) A3 [& IGenes Dev3 y6 b* z9 [7 ^! k* u' u$ U( s! T
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Boman, BM        2008        Human colon cancer stem cells: a new paradigm in gastrointestinal oncology.
0 p+ a- F3 J( {# T+ ~( v6 u3 UJ Clin Oncol" ]$ a% N4 C! S* h, |
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Cammareri, P        2008        Isolation and culture of colon cancer stem cells.
2 P/ c6 d" k% rMethods Cell Biol) W) X5 P; Y! r' q
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Du, L        2008        CD44 is of functional importance for colorectal cancer stem cells.7 Q  t1 m3 _2 L% A+ Y3 W( ~
Clin Cancer Res9 x9 x+ e  K7 f* o
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Dylla, SJ        2008        Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy.. n8 }+ ]) F0 ?( f6 c
PLoS ONE
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Francipane, MG        2008        Crucial role of interleukin-4 in the survival of colon cancer stem cells.
* X& t' K; `. L1 f+ `Cancer Res
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Fre, S        2008        Epithelial morphogenesis and intestinal cancer: new insights in signaling mechanisms.% ~/ p; Q: u: `, l
Adv Cancer Res
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Horst, D        2008        CD133 expression is an independent prognostic marker for low survival in colorectal cancer.) N3 y4 ^; E# {2 t4 U
Br J Cancer
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) W! Q5 z0 b& N- FHuang, EH        2008        Colon cancer stem cells: implications for prevention and therapy.6 O7 S, y: u. V* p8 u! d
Trends Mol Med
" N1 y) h. |9 O: u% a( w: |添加到文献库: 16 Jan 2009上次更新日期: 16 Jan 2009
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Ieta, K        2008        Biological and genetic characteristics of tumor-initiating cells in colon cancer.
3 ~+ ]+ S! k0 {! q: RAnn Surg Oncol! Z* D5 P+ W( K
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Kirkland, SC        2008        {alpha}2{beta}1 Integrin Regulates Lineage Commitment in Multipotent Human Colorectal Cancer Cells.
1 m' d1 F- }$ T4 ^( J) wJ Biol Chem
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3 y, W5 n2 j0 W4 M2 XKreso, A        2008        Colon cancer stem cells.
9 W1 G* d' n/ K6 t8 ]7 L- v* m' @  JCurr Protoc Stem Cell Biol
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LaBarge, MA        2008        Is CD133 a marker of metastatic colon cancer stem cells?
, C! F; l+ s4 h' FJ Clin Invest3 i, \2 X# A/ X' X' T5 h& L
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Le, NH        2008        Tumour-stroma interactions in colorectal cancer: converging on beta-catenin activation and cancer stemness.
! c6 J: i& R0 Q0 B% f/ @* t: _7 sBr J Cancer# O5 k0 ?: n* ?. A/ X- I+ s; y
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Odoux, C        2008        A stochastic model for cancer stem cell origin in metastatic colon cancer.
2 H" [1 V7 C" M0 q! A7 y  G* x6 vCancer Res1 I% k6 m: c* y
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. f7 h3 @# N0 JPohl, A        2008        Stem cells in colon cancer.
: j# O3 R0 |$ l- |8 J9 }Clin Colorectal Cancer, \7 f; B* A6 U* `: D- b. ^) I
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' B$ g- Q/ o- u& U! P  ORicci-Vitiani, L        2008        Colon cancer stem cells.
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Todaro, M        2008        IL-4-mediated drug resistance in colon cancer stem cells.- Z7 }8 }7 \0 R3 x; w) z8 g
Cell Cycle
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van der Flier, LG        2008        Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium.# D' |7 ~: }! Y  p  ]' i
Annu Rev Physiol8 Q2 d& ^8 u4 g& `
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Vermeulen, L        2008        Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.
6 Z7 o0 E5 }; D: D9 gProc Natl Acad Sci U S A
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Willis, ND        2008        Colonic and colorectal cancer stem cells: progress in the search for putative biomarkers.% u, L- B! `* ~- p
J Anat/ n0 ~1 r2 u7 }4 p
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1 k+ Y# o) j; r, E9 i( l0 CXu, M        2008        Monoclonal antibody CC188 binds a carbohydrate epitope expressed on the surface of both colorectal cancer stem cells and their differentiated progeny.% d  q/ n6 |- @6 ~9 W
Clin Cancer Res$ k) ^+ p  |* Q  ~+ P1 ^+ H# y, r
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' n7 C5 g: [, MZhu, L        2008        Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation., T$ O5 }; A7 |! K7 s. b6 r. N! {; p
Nature
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Carpentino, JE        2009        Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer.
- E& x+ Q8 }, j( b6 ^  {Cancer Res
6 U) c3 w$ `/ A) H5 ^$ {添加到文献库: 13 Jan 2010上次更新日期: 13 Jan 2010
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8 `" Z3 P* F/ ?- N; o7 k) PDallas, NA        2009        Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition.
1 e6 i5 J) E; x! S% V. B3 OCancer Res% o+ c( O' S1 D- f5 j( V
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Horst, D        2009        Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer.
- r# A+ x7 }- ]8 u. c$ BCancer Invest
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% H" ^! W6 [5 gHorst, D        2009        The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer.
0 j8 c+ }! K$ `2 V7 U$ X0 [  j+ bJ Pathol# {; \9 r- a5 v+ _1 M2 f7 H
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. r' d' z0 T7 F% _# `2 e$ tHuang, EH        2009        Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis.
3 M& Q& D  N+ f8 R' o+ O/ @Cancer Res
2 |' K1 b; Z1 B& W& m# S添加到文献库: 01 May 2010上次更新日期: 01 May 20105 J2 z/ m& l7 L# h! t
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Kai, K        2009        Maintenance of HCT116 colon cancer cell line conforms to a stochastic model but not a cancer stem cell model.) F3 C  I) J" {$ j. G7 ?
Cancer Sci
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0 F3 @) r2 p) V, QKirkland, SC        2009        Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells.; x! P: F$ V7 |
Br J Cancer# o9 S! G; {6 [, p7 W
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Patel, BB        2009        Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: a risk factor for colon cancer.
( \( U2 |0 F5 X  M9 BBiochem Biophys Res Commun
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Puglisi, MA        2009        Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer.% X) Z- f' k0 b" A" t8 l4 x
Eur Rev Med Pharmacol Sci. g+ w& Y9 S: i2 _& u9 [; M- E( ]
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Ricci-Vitiani, L        2009        Colon cancer stem cells./ |2 R+ [' j/ a. ^" X
J Mol Med
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Saiki, Y        2009        Comprehensive Analysis of the Clinical Significance of Inducing Pluripotent Stemness-Related Gene Expression in Colorectal Cancer Cells.
: L; O- @- D9 t' p; ~- hAnn Surg Oncol8 X- J# L0 p* x2 q& F1 b7 `! z; s; H
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9 w3 x- E' w: h8 k) y* ]Thenappan, A        2009        New Therapeutics Targeting Colon Cancer Stem Cells.
% f* Q/ R  m9 BCurr Colorectal Cancer Rep0 I' T1 t- _5 b- T+ b0 d
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2 Y2 `2 u5 _9 f. G) qTodaro, M        2009        Efficient killing of human colon cancer stem cells by gammadelta T lymphocytes.
  k2 G+ }$ L6 X" OJ Immunol) W: o! U) v& W9 T3 C/ M- A
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0 l  Q% I# E: Zvan der Flier, LG        2009        OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells.
+ P1 {3 e1 o' I; f$ y- v' |Gastroenterology& U$ y# m2 |) t* P' X
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' X6 Q& B( k/ L$ zVarnat, F        2009        Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion.
5 t; s& N8 B$ U/ `EMBO Mol Med* \/ w: }( F& d6 L2 E, P+ Q
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( z4 S  G& t2 o; h' S( t9 T* ]Yeung, TM        2009        Colorectal cancer stem cells.5 N4 E6 W/ Y6 f' X5 M
Dis Colon Rectum4 w8 ]( G" k0 P% I9 @
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+ \! m7 s' J4 [+ x" a; x& VCammareri, P        2010        Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells.
' j- n* G2 F# CCancer Res
% b  ?, |7 D; A8 K3 o' G添加到文献库: 26 Jun 2010上次更新日期: 26 Jun 20101 n. {/ a) m, E
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Fang, DD        2010        Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery.
$ A+ I+ u: z6 s2 ~5 G5 bBr J Cancer4 z) p7 u- \. y# i
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Korkaya, H        2010        Cancer stem cells: nature versus nurture.6 P. p: q6 B: p; `. T- F$ Y
Nat Cell Biol
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- ~6 B7 S0 z+ @# c4 c/ f! `Ku, JL        2010        Establishment and characterization of 13 human colorectal carcinoma cell lines: mutations of genes and expressions of drug-sensitivity genes and cancer stem cell markers.: U  Z' H$ V' n; F! e/ R/ Y
Carcinogenesis
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Pang, R        2010        A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer.* [, [# P7 P1 ?2 T% X; O! G
Cell Stem Cell
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8 [8 q  s* A6 ?* x0 iSikandar, SS        2010        NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer.5 x& m. Q) i- \. C4 {
Cancer Res
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' b1 T8 o% g: |: F4 @* r" }Todaro, M        2010        Colon cancer stem cells: promise of targeted therapy.
/ E( v( _/ J6 Q5 n. MGastroenterology
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! t. }8 K7 ?( a8 M" AVermeulen, L        2010        Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.% W8 l& S: a+ F, r. h& s; O1 X  r
Nat Cell Biol+ J9 C: |0 u  x& R1 t0 }/ ?
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5 t6 f1 H6 V( a: v) G7 r3 `Vermeulen, L        2010        Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
/ D0 A* i  z7 s( _+ LNat Cell Biol" j4 Z  z  b. V- |
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, s' N& {9 n/ M* K5 ]" BWang, YK        2010        Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells.
0 s8 G4 T  Q" c& d8 XCarcinogenesis  t' ~: H  d) X9 S* M( a
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0 ^. z+ ^; f2 X# m, W7 }Yeung, TM        2010        Cancer stem cells from colorectal cancer-derived cell lines.  K6 `2 s; R; b- f" D9 @7 Q
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2 X5 G; `& ~) b: [8 S6 p/ oBuczacki, S.        2011        Stem cells, quiescence and rectal carcinoma: an unexplored relationship and potential therapeutic target.1 q' V1 X3 I0 _/ Q0 M
Br J Cancer
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Chen, K. L.        2011        Highly enriched CD133(+)CD44(+) stem-like cells with CD133(+)CD44(high) metastatic subset in HCT116 colon cancer cells.! R% l5 b. O" \% E* m
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9 i" S0 y2 D  m% [de Sousa, E. M.        2011        Targeting Wnt signaling in colon cancer stem cells.
9 M5 H) m: G1 I6 p5 s4 d1 i0 W0 BClin Cancer Res$ k% j' `" Q$ g- S
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. I) Q. X. |4 b" TEmmink, B. L.        2011        Differentiated human colorectal cancer cells protect tumor-initiating cells from irinotecan.5 o6 {  ]) p4 `( J9 _7 J8 n
Gastroenterology
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Gallmeier, E.        2011        Inhibition of ataxia telangiectasia- and Rad3-related function abrogates the in vitro and in vivo tumorigenicity of human colon cancer cells through depletion of the CD133(+) tumor-initiating cell fraction.' q8 U0 [" o7 Q! x5 G3 c
Stem Cells
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Gavert, N.        2011        L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers.
  l! p: `0 K0 e3 s$ Z' m/ gMol Cancer Res
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Gerger, A.        2011        Common cancer stem cell gene variants predict colon cancer recurrence.7 E! c& @# {, B) h5 `
Clin Cancer Res
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0 C1 M6 R( e2 z( Z7 t0 OHongo, K.        2011        CD133(-) Cells, Derived From a Single Human Colon Cancer Cell Line, Are More Resistant to 5-Fluorouracil (FU) Than CD133(+) Cells, Dependent on the β1-Integrin Signaling.: C, e3 r- _8 f7 P
J Surg Res
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Hwang, W. L.        2011        SNAIL Regulates Interleukin-8 Expression, Stem Cell-Like Activity, and Tumorigenicity of Human Colorectal Carcinoma Cells.6 [' Q; C! q' l  J8 `& G) W, V- l
Gastroenterology
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Iinuma, H.        2011        Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes' stage B and C colorectal cancer.6 h+ G. b1 r1 u% d/ o" l
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+ k. g5 A5 q5 ^6 KInoda, S.        2011        Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells.7 s. o5 e7 ^+ z9 l3 Z
Am J Pathol) Q) K# r6 r' }& O! m) d! [  y
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Nat Med
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# z: m# r+ k! m6 dKannen, V.        2011        The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light.% t) d1 D) l8 N* X8 K+ X7 [5 E
Biochem Biophys Res Commun3 |3 D) O5 n3 p( m( z% Y1 f
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Ma, Y. L.        2011        Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b.* S: w; N9 C6 f3 o
J Cell Mol Med( C0 N: D  b# j. L* ~' F9 X
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) T" K& Z, D7 ?6 f: X: P( pMerlos-Suárez, A.        2011        The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.) C$ e" X  [& j- D5 W; P; Z% k7 z
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& ?7 M! N! X1 z" ?1 W7 n1 _5 ]/ ~) ?Múnera, J.        2011        Ets2 regulates colonic stem cells and sensitivity to tumorigenesis.
, k+ z/ x: Q: ^5 M, CStem Cells) R! |, U! Y1 T2 Z7 w; J" l
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& ?. T' R- O5 z- j6 J  p8 a! e% QNagata, T.        2011        Expression of Cancer Stem Cell Markers CD133 and CD44 in Locoregional Recurrence of Rectal Cancer.
" }9 e( m; ~; V( T. k9 pAnticancer Res
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4 x) s7 D, o3 m' z- [- k, `4 sPapailiou, J.        2011        Stem cells in colon cancer. A new era in cancer theory begins.
# K: H$ ^$ H2 I$ u2 W3 W& |2 FInt J Colorectal Dis
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, \6 v( e, I" i4 p3 b3 v% pRoth, S.        2011        Quiescent stem cells in intestinal homeostasis and cancer.
9 v' ]0 E, I# v5 Y, PCell Commun Adhes# u5 D- i! K* S7 W% Z' V# K
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) c+ O4 R+ c+ ?  W9 M/ fSu, Y. J.        2011        Direct reprogramming of stem cell properties in colon cancer cells by CD44.
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Yu, X. F.        2011        miR-93 suppresses proliferation and colony formation of human colon cancer stem cells.
8 t. F$ D  X$ q6 B8 V8 ~World J Gastroenterol9 k1 W1 P8 r* @  I
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Zeki, S. S.        2011        Stem cells and their implications for colorectal cancer." h) h4 \/ j5 r; H; v* |8 J
Nat Rev Gastroenterol Hepatol
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3 y/ z1 B& Q" NVaiopoulos, A. G.        2012        Colorectal cancer stem cells." r5 o9 ^: Z0 f! l
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板凳
发表于 2012-3-7 08:56 |只看该作者
干细胞之家微信公众号
谢谢了,楼主做的很仔细,标题还特意区分出来,以后查找资料方便了。

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报纸
发表于 2012-3-7 09:36 |只看该作者
回复 csc1981 的帖子
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$ y' J+ E7 i" E$ }5 Y楼主能不能将文献打个包啊
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地板
发表于 2012-10-20 19:56 |只看该作者
准备开始攻读,压力山大啊
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