Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer

被引：231

作者：

Fumagalli, Arianna ^{[1
,8
]}

Oost, Koen C. ^{[1
,2
]}

Kester, Lennart ^{[1
]}

Morgner, Jessica ^{[1
]}

Bornes, Laura ^{[1
]}

Bruens, Lotte ^{[1
,2
]}

Spaargaren, Lisa ^{[1
]}

Azkanaz, Maria ^{[1
]}

Schelfhorst, Tim ^{[1
]}

Beerling, Evelyne ^{[1
]}

Heinz, Maria C. ^{[2
]}

Postrach, Daniel ^{[1
]}

Seinstra, Danielle ^{[1
]}

Sieuwerts, Anieta M. ^{[4
]}

Martens, John W. M. ^{[4
]}

van der Elst, Stefan ^{[5
,6
]}

van Baalen, Martijn ^{[3
]}

Bhowmick, Debajit ^{[3
]}

Vrisekoop, Nienke ^{[7
]}

Ellenbroek, Saskia I. J. ^{[1
]}

Suijkerbuijk, Saskia J. E. ^{[1
]}

Snippert, Hugo J. ^{[2
]}

van Rheenen, Jacco ^{[1
]}

机构：

[1] Netherlands Canc Inst, Oncode Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands

[2] Univ Med Ctr Utrecht, Ctr Mol Med, Mol Canc Res, Oncode Inst, NL-3584 CX Utrecht, Netherlands

[3] Netherlands Canc Inst, Flow Cytometry Facil, NL-1066 CX Amsterdam, Netherlands

[4] Erasmus MC, Erasmus MC Canc Inst, Dept Med Oncol & Canc Genom Netherlands, NL-3015 GD Rotterdam, Netherlands

[5] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, Ctr Translat Immunol, Dept Resp Med, NL-3584 EA Utrecht, Netherlands

[8] Princess Maxima Ctr Pediat Oncol, Oncode Inst, NL-3584 CS Utrecht, Netherlands

来源：

CELL STEM CELL | 2020年 / 26卷 / 04期

基金：

欧盟地平线“2020”; 欧洲研究理事会;

关键词：

STEM-CELLS; TUMOR-GROWTH; TRANSPLANTATION; HETEROGENEITY; POPULATION; REVEALS; EMT;

D O I：

10.1016/j.stem.2020.02.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：569 / +

页数：17

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