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Science:肠腺瘤中的肿瘤干细胞

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8月1日,<em>Science</em>杂志在线报道了肠腺瘤肿瘤干细胞的最新研究进展。 认为肿瘤是由特定的干细胞种群所驱动的,所谓的癌症干细胞假说,已经引发了极大的关注和争议。对小鼠模型的研究证实,在原发性肠腺瘤中存在着干细胞。 <!--more--> 通过使用多色的Cre-reporter R26R-Confetti报告者系统,进行肿瘤细胞...
8月1日,<em>Science</em>杂志在线报道了肠腺瘤肿瘤干细胞的最新研究进展。

认为肿瘤是由特定的干细胞种群所驱动的,所谓的癌症干细胞假说,已经引发了极大的关注和争议。对小鼠模型的研究证实,在原发性肠腺瘤中存在着干细胞。

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通过使用多色的Cre-reporter R26R-Confetti报告者系统,进行肿瘤细胞的"家系追溯",研究者证明,隐窝干细胞标记物LGR5(富含亮氨酸重复序列,含有异鸟嘌呤核苷酸结合蛋白的偶联受体5),也标志着肠腺瘤细胞一个亚群,该亚群细胞推动着肠腺瘤的生长。

这些LGR5+细胞,约占腺瘤细胞的5至10%。它们可产生新的LGR5+细胞以及其他所有类型的肠腺瘤细胞。 LGR5+细胞混杂在腺瘤基底部附近的潘氏细胞之中,类似于正常隐窝微环境的架构模式。 
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080308320212.jpg" alt="" width="113" height="149" border="0" hspace="0" />

<a title="" href="http://dx.doi.org/10.1016/j.cell.2011.10.017" target="_blank">doi:</a><a title="" href="http://www.sciencemag.org/content/early/2012/07/31/science.1224676" target="_blank">10.1016/j.cell.2011.10.017</a>
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<br/><strong>Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas</strong><br/>


Arnout G. Schepers*,Hugo J. Snippert*,?,Daniel E. Stange,Maaike van den Born,Johan H. van Es,Marc van de Wetering,Hans Clevers?

The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By “lineage retracing” using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat–containing heterotrimeric guanine nucleotide–binding protein–coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5+ cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5+ cells as well as all other adenoma cell types. The Lgr5+ cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche.

<br/>来源:生物谷

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