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CD38 in cancer-associated fibroblasts promotes pro-tumoral activity
Lab Invest. 2020 Dec;100(12) :1517-1531
PMID: 32612286 PMCID: PMC7686132 URL: https://www.ncbi.nlm.nih.gov/pubmed/32612286
AbstractPrimary and metastatic melanoma progression are supported by a local microenvironment comprising, inter alia, of cancer-associated fibroblasts (CAFs). We previously reported in orthotropic/syngeneic mouse models that the stromal ectoenzyme CD38 participates in melanoma growth and metastasis. The results presented here suggest that CD38 is a novel regulator of CAFs' pro-tumorigenic functions. Orthotopic co-implantation of CD38 deficient fibroblasts and B16F10 melanoma cells limited tumor size, compared with CD38-expressing fibroblasts. Intrinsically, CAF-CD38 promoted migration of primary fibroblasts toward melanoma cells. Further, in vitro paracrine effects of CAF-CD38 fostered tumor cell migration and invasion as well as endothelial cell tube formation. Mechanistically, we report that CAF-CD38 drives the protein expression of an angiogenic/pro-metastatic signature, which includes VEGF-A, FGF-2, CXCL-12, MMP-9, and HGF. Data suggest that CAF-CD38 fosters tumorigenesis by enabling the production of pro-tumoral factors that promote cell invasion, migration, and angiogenesis.
Notes1530-0307 Ben Baruch, Bar Mantsur, Einav Franco-Barraza, Janusz Orcid: 0000-0003-3652-5311 Blacher, Eran Orcid: 0000-0003-3207-0153 Cukierman, Edna Orcid: 0000-0002-1452-9576 Stein, Reuven Orcid: 0000-0002-7166-6542 R21CA231252/U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ R01 CA232256/CA/NCI NIH HHS/United States 0604912701/TAU | Cancer Biology Research Center, Tel Aviv University (CBRC, TAU)/ CA06927/U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ R01CA232256/U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ P30 CA006927/CA/NCI NIH HHS/United States Journal Article United States Lab Invest. 2020 Jul 1. doi: 10.1038/s41374-020-0458-8.