The Involvement of PDGF-B/PDGFRβ Axis in the Resistance to Antiangiogenic and Antivascular Therapy in Renal Cancer

• Published in: Anticancer research 2016-05, Vol.36 (5), p.2291-2295
• Main Authors: Cumpănas, Alin Adrian, Cimpean, Anca Maria, Ferician, Ovidiu, Ceausu, Raluca Amalia, Sarb, Simona, Barbos, Vlad, Dema, Alice, Raica, Marius
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Antineoplastic Agents - pharmacology; Carcinoma, Renal Cell - blood supply; Carcinoma, Renal Cell - chemistry; Carcinoma, Renal Cell - drug therapy; Drug Resistance, Neoplasm - physiology; Humans; Kidney Neoplasms - blood supply; Kidney Neoplasms - chemistry; Kidney Neoplasms - drug therapy; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-sis - analysis; Proto-Oncogene Proteins c-sis - physiology; Receptor, Platelet-Derived Growth Factor beta - analysis; Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors; Receptor, Platelet-Derived Growth Factor beta - physiology; Retrospective Studies; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - physiology
• ISSN: 1791-7530

Studies developed in the field of platelet-derived growth factors/platelet-derived growth factor receptors (PDGFs/PDGFRs) inhibition have focused on the therapeutic effects on tumor cells, neglecting their potential effects on tumor blood vessels. We herein propose a differential and critic assessment of platelet-derived growth factor B (PDGF-B) and platelet-derived growth factor receptor β (PDGFRβ) in renal cell carcinoma, correlated with the four main vascular patterns previously reported by our team. PDGF-B and PDGFRβ were evaluated on 50 archival paraffin embedded specimens related to vascular endothelial growth factor (VEGF), its inhibitory isoform VEGF165b and vascular patterns. Our results support the involvement of VEGF165b in the phosphorylation of PDGFRβ with an inhibitory effect on endothelial proliferation and migration. The simultaneous action of PDGF-B/PDGFRβ and VEGF165b on the same type of receptor may explain the resistance to antiangiogenic therapy, which depends on the degree of modulation of PDGFRβ phosphorylation.