日本在世界上首次人工制成癌干细胞

细胞海洋

2012年06月08日     来源：科技部
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! D7 R5 d1 e% u癌干细胞是生成癌细胞的源泉，日本冈山大学研究生院妹尾昌治教授（生物工学）的研究小组成功利用诱导性多能干细胞（iPS细胞）人工制成癌干细胞并在小鼠身上得到验证。此次人工制成癌干细胞属于世界首次，相关研究成果发表于美国科学期刊《PLoS ONE》。& T' C( C/ H& K# s! C. Y+ `9 @# H
  
9 Y" O" |2 i% ]  |# F' b    癌由少量的癌干细胞与普通癌细胞构成。抗癌剂及放射治疗容易杀灭普通癌细胞，但是对于杀灭癌干细胞效果不佳，因此，癌干细胞是癌症复发的重要因素。利用此次的研究成果，进一步研究将癌干细胞作为标的，则有望开创出癌症治疗的新方法。
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6 }% v! Q. @- G5 T) P    妹尾教授的研究小组在培养小鼠iPS细胞的容器中加入普通癌细胞增殖培养液，模拟出生物体内相似的癌症环境，成功地在容器内生成癌干细胞。将人工生成的癌干细胞移植到小鼠皮下，最终产生恶性肿瘤。  
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Donnies

干细胞具有无限自我更新能力，而针对杀死癌干细胞为目标的治疗，应该会能从根本上抑制癌细胞的扩散。

FreeCell

嘻嘻，流氏说iPS就是人造肿瘤！http://www.stemcell8.cn/forum-re ... 635-pid-651896.html
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sunsong7

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5 f/ G4 j' z; G. e& Idoi:10.1371/journal.pone.0033544* P8 j' U( p: K' K/ N) ]
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A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells
: G% }0 C/ {! uLing Chen1,2,3, Tomonari Kasai1, Yueguang Li4, Yuh Sugii1, Guoliang Jin1, Masashi Okada1, Arun Vaidyanath1, Akifumi Mizutani1, Ayano Satoh5, Takayuki Kudoh1, Mary J. C. Hendrix6, David S. Salomon7, Li Fu8*, Masaharu Seno1*
! p0 {. p1 s5 E+ w5 A' vCancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5′-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.8 X, \. T& @. {0 S

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【扩展阅读】
3 z2 Y' s! y* p5 z' D6 ^7 D0 }2 [  E肿瘤干细胞是癌进化的终点而非起点 http://www.stemcell8.cn/thread-46105-1-1.html
4 s  m5 O' [" O" A- U如何制造癌细胞？http://www.stemcell8.cn/thread-54304-1-1.html
$ W' C' \, _3 X: o+ E, qniche reprogramming  http://www.stemcell8.cn/thread-40755-1-1.html
9 ]. O' v2 z2 v. D7 k4 |癌细胞的发生可能是一种“返祖”现象？ http://www.stemcell8.cn/thread-32073-1-1.html0 H5 D+ |6 f& F
遗传物质研究是解决肿瘤问题的方向性错误 http://www.stemcell8.cn/thread-39452-1-1.html& D% ^8 i& I( H. r
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redmaple

赫赫，我们实验室的结果。

playboy723

呵呵  这个挺有意思的   得好好考虑一下：
8 r3 G) S+ F0 `8 _! h; M$ J3 l( j1、ips细胞与csc的区别，这个往深里讲就涉及到肿瘤的来源问题0 a$ B( G- A& w
2、从ips培养成肿瘤细胞的过程中，细胞基因水平发生的哪些变化，换句话讲肿瘤的产生是由于传代过程中基因突变造成的还是仅仅是细胞类型的转换& z1 r. g$ \% y6 Y7 G8 L; I
3、我想确认的是：是否这个实验从侧面证明了肿瘤是一种代谢性疾病？  之前的二次突变学说是否还成立？
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redmaple

看到大家讨论这个问题，感觉很高兴，说明很多人对此感兴趣。ips细胞和csc还是有些差别的，都是干细胞，也都高表达干细胞的marker，保留干细胞的特征，又有区别，那就是成瘤能力；ips在分化成肿瘤细胞的过程中，基因肯定是发生变化的，通过基因芯片和real time也证实了这一点。