Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer
Publication date
2020-04-02
Authors
Fumagalli, Arianna
Oost, Koen C.
Kester, Lennart A
Morgner, Jessica
Bornes, Laura
Bruens, Lotte
Spaargaren, Lisa
Azkanaz, Maria
Schelfhorst, Tim
Beerling, Evelyne
Editors
Advisors
Supervisors
Document Type
Article
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cc_by
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.
Keywords
cancer stem cells, circulating tumor cells, colorectal cancer, intravital microscopy, Lgr5, metastasis, microenvironment, plasticity, Molecular Medicine, Genetics, Cell Biology
Citation
Fumagalli, A, Oost, K C, Kester, L, Morgner, J, Bornes, L, Bruens, L, Spaargaren, L, Azkanaz, M, Schelfhorst, T, Beerling, E, Heinz, M C, Postrach, D, Seinstra, D, Sieuwerts, A M, Martens, J W M, van der Elst, S, van Baalen, M, Bhowmick, D, Vrisekoop, N, Ellenbroek, S I J, Suijkerbuijk, S J E, Snippert, H J & van Rheenen, J 2020, 'Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer', Cell stem cell, vol. 26, no. 4, pp. 569-578.e7. https://doi.org/10.1016/j.stem.2020.02.008