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Comment
. 2020 Apr 2;26(4):469-471.
doi: 10.1016/j.stem.2020.03.007.

Plasticity in Motion: Shape-Shifting Lgr5-Cells Initiate Colorectal Cancer Metastasis

Karuna Ganesh  1
Affiliations
Comment

Plasticity in Motion: Shape-Shifting Lgr5-Cells Initiate Colorectal Cancer Metastasis

Karuna Ganesh. Cell Stem Cell. .

Abstract

In this issue of Cell Stem Cell, Fumagalli et al. (2020) employ intravital microscopy of colorectal cancer organoid xenografts to investigate the cell of origin of metastases. While tumor-initiating cells are Lgr5+, most disseminated cancer cells are Lgr5- and seed liver metastases in which Lgr5+ cells then appear, showing that bidirectional plasticity of phenotypic states drives metastasis.

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Figures

Figure 1.
Figure 1.
Plasticity of Lgr5– Cells Initiates Colorectal Cancer Metastasis Organoid-derived orthotopic tumor xenografts are initiated by eGFP+Lgr5+ cells (green), which generate eGFP−Lgr5− (red) differentiated progeny. The majority of cells invading the stroma, disseminating via the portal vein, or seeding liver metastasis are eGFP−Lgr5− (red). Liver metastasis is initiated by eGFP−Lgr5− (red) cells, a subset of which undergo plasticity to generate eGFP+Lgr5+ cells (green). Diphtheria-toxin-driven ablation of Lgr5DTR/eGFP cells causes collapse of orthotopic cecal tumors and regression of liver metastases. Bidirectional plasticity of Lgr5 cells is required to initiate and propagate CRC metastases.
See this image and copyright information in PMC

Comment on

  • Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer.
    Fumagalli A, Oost KC, Kester L, Morgner J, Bornes L, Bruens L, Spaargaren L, Azkanaz M, Schelfhorst T, Beerling E, Heinz MC, Postrach D, Seinstra D, Sieuwerts AM, Martens JWM, van der Elst S, van Baalen M, Bhowmick D, Vrisekoop N, Ellenbroek SIJ, Suijkerbuijk SJE, Snippert HJ, van Rheenen J. Fumagalli A, et al. Cell Stem Cell. 2020 Apr 2;26(4):569-578.e7. doi: 10.1016/j.stem.2020.02.008. Epub 2020 Mar 12. Cell Stem Cell. 2020. PMID: 32169167 Free PMC article.

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