Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer
Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer
复制标题
Lgr5阴性癌细胞的可塑性驱动结直肠癌转移
DOI：
10.1016/j.stem.2020.02.008
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发表时间：
2020-04-02
期刊：
影响因子：
23.9
通讯作者：
van Rheenen, Jacco
中科院分区：
文献类型：
--
作者：
Fumagalli, Arianna;Oost, Koen C.;van Rheenen, Jacco
结肠直肠癌干细胞（CSC）表达Lgr 5，并显示出广泛的干细胞样多能性和自我更新，并被认为是转移性疾病的种子。在这里，我们使用了结肠直肠癌（CRC）和人类肿瘤异种移植物的小鼠模型来研究转移的起源细胞。我们发现循环中大多数播散的CRC细胞是Lgr 5（-），并形成远处转移，其中出现Lgr 5（+）CSC。这种可塑性的发生独立于干诱导的微生物学因素，是不可缺少的产物，但不是建立，转移。总之，这些发现表明，大多数结直肠癌转移是由Lgr 5（-）细胞接种的，Lgr 5（-）细胞表现出以非生态位依赖性方式成为CSC的内在能力，并可以恢复转移性肿瘤中的上皮层次。
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 microenviron-mental 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.