TY - JOUR
T1 - CD38 in cancer-associated fibroblasts promotes pro-tumoral activity
AU - Ben Baruch, Bar
AU - Mantsur, Einav
AU - Franco-Barraza, Janusz
AU - Blacher, Eran
AU - Cukierman, Edna
AU - Stein, Reuven
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.
PY - 2020/12
Y1 - 2020/12
N2 - Primary 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.
AB - Primary 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.
UR - http://www.scopus.com/inward/record.url?scp=85087306172&partnerID=8YFLogxK
U2 - 10.1038/s41374-020-0458-8
DO - 10.1038/s41374-020-0458-8
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C2 - 32612286
AN - SCOPUS:85087306172
SN - 0023-6837
VL - 100
SP - 1517
EP - 1531
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 12
ER -
