Journal
CELL STEM CELL
Volume 26, Issue 4, Pages 569-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2020.02.008
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Funding
- Dutch Cancer Society Fellowship [BUIT2013-5847]
- European Molecular Biology Organization (EMBO) fellowship [ALTF 202-2016]
- Netherlands Organization of Scientific Research (NWO) (Veni grant) [863.15.011]
- CancerGenomics.nl
- European Research Council [CANCERRECURRENCE 648804]
- Doctor Josef Steiner Foundation
- European Union's Horizon 2020 research and innovation program under Marie Sk1odowska-Curie grant [642866]
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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.
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