结肠癌干细胞与微环境调控

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Nature Cell Biology 12, 468 - 476 (2010) ! ~: l! f7 i+ c4 \, `
Published online: 25 April 2010 | doi:10.1038/ncb2048/ l  I0 |/ B4 {4 k$ j  X2 n5 h0 g) Q& G% y
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. k9 X5 S. u" H+ ^Wnt activity defines colon cancer stem cells and is regulated by the microenvironment
: f9 H2 O) \; y* e5 d; z9 g) K3 [Louis Vermeulen1,5, Felipe De Sousa E Melo1,5, Maartje van der Heijden1, Kate Cameron1, Joan H. de Jong1, Tijana Borovski1, Jurriaan B. Tuynman1, Matilde Todaro2, Christian Merz3, Hans Rodermond1, Martin R. Sprick1, Kristel Kemper1, Dick J. Richel1, Giorgio Stassi2,4 & Jan Paul Medema1
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8 q3 Z* _) W& f3 H6 KAbstractDespite the presence of mutations in APC or β-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when β-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 β-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.- Z& Z: k" e4 |3 n3 L
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+ a" X/ {4 [: L4 mLaboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  J0 {; ?4 p) C' |: ?; ?Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, 90127 Palermo, Italy.
! l: z7 i& X+ }: F* w9 B' NAPOGENIX GmbH, 69120 Heidelberg, Germany.
3 D) t: }+ B3 l9 WPresent address: Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, 27100 Pavia, Italy.% p' I( n" i) y5 ~- Q" @
These authors contributed equally to this work.9 F8 E% T8 x% V: U4 X" D6 C
Correspondence to: Jan Paul Medema1 e-mail: J.P.Medema@amc.uva.nl

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回复 4# ganxibao11 ( w2 t% m) {" G; z$ s% M9 O
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关于你提的观点我并不赞同，首先，本文是在承认肿瘤干细胞假说的前提下做的。你说的第一点，肿瘤本身具有干细胞特性。我想你可能没有注意到，作者文中用的原代细胞都是用cancer stem cell 培养方式富集出来的肿瘤干细胞，然后再用于文中的各个实验。第二点：文中的观点的确是说微环境能使非肿瘤干细胞这群细胞转变为部分具有肿瘤干细胞特性的细胞群体，但并不表示就是反驳肿瘤干细胞假说。文中也没有提到任何质疑的语句。