Effect of platelet-derived growth factor-B on renal cell carcinoma growth and progression.

ABSTRACT

BACKGROUND: Platelet-derived growth factor-B (PDGF-B) expression promotes the proliferation of mural cells surrounding the blood vessels during angiogenesis. The effect of PDGF-B involved in angiogenesis on tumor growth and progression in clear cell renal cell carcinoma (ccRCC) is unknown. METHODS: We examined the expression of PDGF-B and its receptor PDGFR-ß in 174 patients with ccRCC by microarray analysis. Cancer-specific survival was estimated using the Kaplan-Meier method. PDGF-B-transfected and mock-transfected ACHN cells were implanted into mice to induce tumor formation and tumor growth, respectively, and progression in mice models was assessed using immunohistochemistry and histomorphology. The role of PDGF-B during angiogenesis in vitro was evaluated by flow cytometry analysis, cell migration, and tube formation assay. RESULTS: High expression of PDGF-B was associated with significantly decreased risk of cancer-specific mortality (P ≤ 0.001). The data indicated significant inhibition of tumor growth (P ≤ 0.05) and a reduction in proliferating tumor cells (P = 0.019) in vivo. PDGF-B also inhibits tumor metastasis and invasion events in tumor-bearing mice models. In vitro studies revealed that the tube formation capability of vascular smooth muscle cells (VSMCs), which are believed to be the precursors to pericytes in vivo, significantly induced by PDGF-B. The PDGF-B overexpression also results in a tendency to reside in S and G2/M phases of the cell cycle (P = 0.001) and increasing migration capability of VSMCs (P ≤ 0.001). CONCLUSION: Our results demonstrated that PDGF-B, which increased VSMCs proliferation and migration capability during angiogenesis, limited tumor growth and progression in ccRCC. Therefore, PDGF-B may be a novel and promising prognostic marker.