[PDF][PDF] PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment

Y Crawford, I Kasman, L Yu, C Zhong, X Wu… - Cancer cell, 2009 - cell.com
Y Crawford, I Kasman, L Yu, C Zhong, X Wu, Z Modrusan, J Kaminker, N Ferrara
Cancer cell, 2009cell.com
Tumor-or cancer-associated fibroblasts (TAFs or CAFs) from different tumors exhibit distinct
angiogenic and tumorigenic properties. Unlike normal skin fibroblasts or TAFs from TIB6
tumors that are sensitive to anti-VEGF treatment (TAF-TIB6), TAFs from resistant EL4 tumors
(TAF-EL4) can stimulate TIB6 tumor growth even when VEGF is inhibited. We show that
platelet-derived growth factor C (PDGF-C) is upregulated in TAFs from resistant tumors.
PDGF-C-neutralizing antibodies blocked the angiogenesis induced by such TAFs in vivo …
Summary
Tumor- or cancer-associated fibroblasts (TAFs or CAFs) from different tumors exhibit distinct angiogenic and tumorigenic properties. Unlike normal skin fibroblasts or TAFs from TIB6 tumors that are sensitive to anti-VEGF treatment (TAF-TIB6), TAFs from resistant EL4 tumors (TAF-EL4) can stimulate TIB6 tumor growth even when VEGF is inhibited. We show that platelet-derived growth factor C (PDGF-C) is upregulated in TAFs from resistant tumors. PDGF-C-neutralizing antibodies blocked the angiogenesis induced by such TAFs in vivo, slowed the growth of EL4 and admixture (TAF-EL4 + TIB6) tumors, and exhibited additive effects with anti-VEGF-A antibodies. Hence, our data reveal an additional mechanism for TAF-mediated tumorigenesis and suggest that some tumors may overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C.
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