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Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer
- Source :
- Cell Stem Cell, 26(4), 569-578. Cell Press, Cell Stem Cell
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Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • 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<br />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.
- Subjects :
- cancer stem cells
Colorectal cancer
Cell of origin
colorectal cancer
circulating tumor cells
Biology
Article
Receptors, G-Protein-Coupled
Metastasis
Lgr5
03 medical and health sciences
0302 clinical medicine
Circulating tumor cell
SDG 3 - Good Health and Well-being
Cancer stem cell
intravital microscopy
Genetics
medicine
metastasis
Humans
030304 developmental biology
0303 health sciences
LGR5
Cell Biology
medicine.disease
microenvironment
plasticity
Colonic Neoplasms
Cancer cell
Neoplastic Stem Cells
Cancer research
Molecular Medicine
Stem cell
Colorectal Neoplasms
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 19345909
- Volume :
- 26
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Stem Cell
- Accession number :
- edsair.doi.dedup.....95f1b441d63a165850d5378d2acc7bb6
- Full Text :
- https://doi.org/10.1016/j.stem.2020.02.008