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

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

doi:10.1016/j.stem.2020.02.008

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

Arianna Fumagalli
, Koen Oost
, Lennart Kester
, Jessica Morgner
, Laura Bornes
, Lotte Bruens
, Lisa Spaargaren
, Maria Azkanaz
, Tim Schelfhorst
, Evelyne Beerling
, Maria Heinz
, Daniel Postrach
, Danielle Seinstra
, Anieta Sieuwerts
, John Martens
, Stefan van der Elst
, Martijn van Baalen
, Debajit Bhowmick
, N. Vrisekoop
, Saskia Ellenbroek

Saskia Suijkerbuijk, Hugo J G Snippert, Jacco van Rheenen

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Journal	Cell Stem Cell
DOIs	https://doi.org/10.1016/j.stem.2020.02.008
Publication status	Published - 12 Mar 2020
Externally published	Yes

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Fumagalli, A., Oost, K., Kester, L., Morgner, J., Bornes, L., Bruens, L., Spaargaren, L., Azkanaz, M., Schelfhorst, T., Beerling, E., Heinz, M., Postrach, D., Seinstra, D., Sieuwerts, A., Martens, J., van der Elst, S., van Baalen, M., Bhowmick, D., Vrisekoop, N., ... van Rheenen, J. (2020). Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer. Cell Stem Cell. https://doi.org/10.1016/j.stem.2020.02.008

@article{454be307ca1a4c558b81d5c7313d0cb9,

title = "Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer.",

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.",

author = "Arianna Fumagalli and Koen Oost and Lennart Kester and Jessica Morgner and Laura Bornes and Lotte Bruens and Lisa Spaargaren and Maria Azkanaz and Tim Schelfhorst and Evelyne Beerling and Maria Heinz and Daniel Postrach and Danielle Seinstra and Anieta Sieuwerts and John Martens and \{van der Elst\}, Stefan and \{van Baalen\}, Martijn and Debajit Bhowmick and N. Vrisekoop and Saskia Ellenbroek and Saskia Suijkerbuijk and Snippert, \{Hugo J G\} and \{van Rheenen\}, Jacco",

year = "2020",

month = mar,

day = "12",

doi = "10.1016/j.stem.2020.02.008",

language = "English",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

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Fumagalli, A, Oost, K, Kester, L, Morgner, J, Bornes, L, Bruens, L, Spaargaren, L, Azkanaz, M, Schelfhorst, T, Beerling, E, Heinz, M, Postrach, D, Seinstra, D, Sieuwerts, A, Martens, J, van der Elst, S, van Baalen, M, Bhowmick, D, Vrisekoop, N, Ellenbroek, S, Suijkerbuijk, S, Snippert, HJG & van Rheenen, J 2020, 'Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer.', Cell Stem Cell. https://doi.org/10.1016/j.stem.2020.02.008

TY - JOUR

T1 - Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer.

AU - Fumagalli, Arianna

AU - Oost, Koen

AU - Kester, Lennart

AU - Morgner, Jessica

AU - Bornes, Laura

AU - Bruens, Lotte

AU - Spaargaren, Lisa

AU - Azkanaz, Maria

AU - Schelfhorst, Tim

AU - Beerling, Evelyne

AU - Heinz, Maria

AU - Postrach, Daniel

AU - Seinstra, Danielle

AU - Sieuwerts, Anieta

AU - Martens, John

AU - van der Elst, Stefan

AU - van Baalen, Martijn

AU - Bhowmick, Debajit

AU - Vrisekoop, N.

AU - Ellenbroek, Saskia

AU - Suijkerbuijk, Saskia

AU - Snippert, Hugo J G

AU - van Rheenen, Jacco

PY - 2020/3/12

Y1 - 2020/3/12

N2 - 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.

AB - 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.

UR - https://europepmc.org/articles/PMC7118369

U2 - 10.1016/j.stem.2020.02.008

DO - 10.1016/j.stem.2020.02.008

M3 - Article

C2 - 32169167

SN - 1934-5909

JO - Cell Stem Cell

JF - Cell Stem Cell

ER -

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

Abstract

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