8月1日,Science雜志在線報(bào)道了腸腺瘤腫瘤干細(xì)胞的最新研究進(jìn)展,。
認(rèn)為腫瘤是由特定的干細(xì)胞種群所驅(qū)動(dòng)的,,所謂的癌癥干細(xì)胞假說(shuō),已經(jīng)引發(fā)了極大的關(guān)注和爭(zhēng)議,。對(duì)小鼠模型的研究證實(shí),,在原發(fā)性腸腺瘤中存在著干細(xì)胞。
通過(guò)使用多色的Cre-reporter R26R-Confetti報(bào)告者系統(tǒng),,進(jìn)行腫瘤細(xì)胞的"家系追溯",,研究者證明,隱窩干細(xì)胞標(biāo)記物L(fēng)GR5(富含亮氨酸重復(fù)序列,,含有異鳥(niǎo)嘌呤核苷酸結(jié)合蛋白的偶聯(lián)受體5),,也標(biāo)志著腸腺瘤細(xì)胞一個(gè)亞群,該亞群細(xì)胞推動(dòng)著腸腺瘤的生長(zhǎng),。
這些LGR5+細(xì)胞,,約占腺瘤細(xì)胞的5至10%。它們可產(chǎn)生新的LGR5+細(xì)胞以及其他所有類型的腸腺瘤細(xì)胞,。 LGR5+細(xì)胞混雜在腺瘤基底部附近的潘氏細(xì)胞之中,,類似于正常隱窩微環(huán)境的架構(gòu)模式。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas
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.