小柯机器人

荷兰癌症研究所Jacco van Rheenen研究组取得一项新进展，他们的最新工作表明，Lgr5阴性癌细胞的可塑性能够驱动结直肠癌的转移。该研究于2020年3月12日在线发表于《细胞—干细胞》杂志。

研究人员使用了结直肠癌（CRC）和人类肿瘤异种移植的小鼠模型来研究转移灶细胞。他们发现循环中大多数散布的CRC细胞为Lgr5^-，并形成了远处转移灶，其中出现了Lgr5⁺肿瘤干细胞（CSC）。这种可塑性不依赖于干性诱导的微环境因素，并且对于转移的生长而非转移的建立是必不可少的。因此，这些发现表明，大多数结直肠癌转移灶都是由Lgr5^-细胞传播的，这些细胞显示出不依赖于微环境而成为CSC的本质能力，并且可以在转移性肿瘤中重建上皮层级。

据介绍，结直肠CSC表达Lgr5，并表现出大量的干细胞样多能性和自我更新能力，被认为是转移性疾病的种子。

附：英文原文

Author: Arianna Fumagalli, Koen C. Oost, Lennart Kester, Jessica Morgner, Laura Bornes, Lotte Bruens, Lisa Spaargaren, Maria Azkanaz, Tim Schelfhorst, Evelyne Beerling, Maria C. Heinz, Daniel Postrach, Danielle Seinstra, Anieta M. Sieuwerts, John W.M. Martens, Stefan van der Elst, Martijn van Baalen, Debajit Bhowmick, Nienke Vrisekoop, Saskia I.J. Ellenbroek, Saskia J.E. Suijkerbuijk, Hugo J. Snippert, Jacco van Rheenen

Issue&Volume: 2020-03-12

Abstract: Colorectal cancer stem cells (CSCs) express Lgr5 and display extensive stem cell-like multipotency and self-renewal and are thought to seed metastatic disease. Here, we used a mouse model of colorectal cancer (CRC) and human tumor xenografts to investigate the cell of origin of metastases. We found that most disseminated CRC cells in circulation were Lgr5 and formed distant metastases in which Lgr5+ CSCs appeared. This plasticity occurred independently of stemness-inducing microenvironmental factors and was indispensable for outgrowth, but not establishment, of metastases. Together, these findings show that most colorectal cancer metastases are seeded by Lgr5 cells, which display intrinsic capacity to become CSCs in a niche-independent manner and can restore epithelial hierarchies in metastatic tumors.

DOI: 10.1016/j.stem.2020.02.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30061-8

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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