Abstract
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.
MeSH terms
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Animals
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Antibodies / immunology
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Antibodies / therapeutic use*
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CD11b Antigen / metabolism
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Separation
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Cell Transformation, Neoplastic / immunology
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology*
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Cells, Cultured
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Chemokine CXCL12 / metabolism
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Disease Progression
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Drug Resistance, Neoplasm / drug effects
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Fibroblasts / metabolism*
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Fibroblasts / pathology
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Humans
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Immunotherapy
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Lymphokines / metabolism*
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Mice
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Mice, Nude
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Neoplasm Transplantation
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / immunology
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / pathology
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Platelet-Derived Growth Factor / metabolism*
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Up-Regulation
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Vascular Endothelial Growth Factor A / immunology*
Substances
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Antibodies
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CD11b Antigen
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Lymphokines
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Platelet-Derived Growth Factor
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Vascular Endothelial Growth Factor A
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platelet-derived growth factor C