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.

大肠癌干细胞（CSC）表达Lgr5，并显示出广泛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。在这里，我们使用了结直肠癌（CRC）和人类肿瘤异种移植物的小鼠模型来研究转移灶的细胞。我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，其中出现了Lgr5 ⁺ CSC。这种可塑性独立于诱导茎的微环境因素而发生，并且对于转移的生长而不是转移的建立是必不可少的。在一起，这些发现表明大多数结肠直肠癌转移是由Lgr5播种的^- 细胞具有内在的能力，能以利基独立的方式成为CSC，并能恢复转移性肿瘤的上皮层级。