Fibroblasts associated with tumors refractory to anti-VEGF treatment
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ABSTRACT: PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment Tumor associated fibroblasts (TAF) from different tumors exhibit distinct angiogenic and tumorigenic properties. Unlike normal skin fibroblasts (NSF) or TAF (TAF-TIB6) from TIB6 tumors that are sensitive to anti-VEGF treatment, TAF (TAF-EL4) from resistant EL4 tumors can stimulate TIB6 tumor growth even when VEGF is inhibited. We show that platelet-derived growth factor (PDGF)-C is upregulated in TAFs from resistant tumors. PDGF-C neutralizing antibodies blocked the angiogenesis induced by such TAF in vivo and slowed the growth of EL4 and admixture (TAF-EL4 + TIB6) tumors and exhibited additive effects with anti-VEGF-A antibodies. Hence, our data reveal a novel mechanism for TAF mediated tumorigenesis and suggest that some tumors may overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C
ORGANISM(S): Mus musculus
PROVIDER: GSE13549 | GEO | 2009/01/05
SECONDARY ACCESSION(S): PRJNA110729
REPOSITORIES: GEO
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