Details

Autor(en) / Beteiligte

• Fumagalli, Arianna
• Oost, Koen C.
• Kester, Lennart
• Morgner, Jessica
• Bornes, Laura
• Bruens, Lotte
• Spaargaren, Lisa
• Azkanaz, Maria
• Schelfhorst, Tim
• Beerling, Evelyne
• Heinz, Maria C.
• Postrach, Daniel
• Seinstra, Danielle
• Sieuwerts, Anieta M.
• Martens, John W.M.
• van der Elst, Stefan
• van Baalen, Martijn
• Bhowmick, Debajit
• Vrisekoop, Nienke
• Ellenbroek, Saskia I.J.
• Suijkerbuijk, Saskia J.E.
• Snippert, Hugo J.
• van Rheenen, Jacco

Titel

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

Ist Teil von

• Cell stem cell, 2020-04, Vol.26 (4), p.569-578.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •The majority of disseminating cells of colorectal cancer are Lgr5−•Lgr5− cancer cells are the main seeds of colorectal cancer metastatic lesions•Long-term metastatic growth from Lgr5− cells requires appearance of Lgr5+ cells•Lgr5− metastases have the intrinsic capacity to re-establish the cellular hierarchy Van Rheenen and colleagues study Lgr5+ cancer stem cells during colorectal cancer metastasis. They demonstrate that the majority of metastases are seeded by Lgr5− cells, which upon arrival seed metastases in which Lgr5+ cells appear. This plasticity can occur independently of stemness-inducing factors and is indispensable for long-term metastatic growth.