Inhibition of angiogenesis via FGF-2 blockage in primitive and bone metastatic renal cell carcinoma

Abstract

Background: Fibroblast growth factor-2 (FGF-2) has a role in the angiogenesis induced by renal carcinoma.

Materials and methods: Blockage of FGF-2 by an antisense oligonucleotide (ASO) or by a mouse neutralizing anti-human FGF-2 monoclonal antibody (anti-FGF-2-mAb) was evaluated on a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990), on Caki-1 and ACHN cells. Cocultures of endothelial cells and ASO- or mAb-treated carcinoma lines were investigated.

Results: Anti-FGF-2-mAb treatment induced a 33% reduction of FGF-2 released by ACHN, a 31% reduction of FGF-2 released by Caki-1, and a 70% reduction of FGF-2 released by CRBM-1990. ASO treatment did not inhibit endothelial cell proliferation. In contrast, anti-FGF-2-mAb significantly decreased endothelial cells proliferation induced by ACHN and CRBM-1990. The inhibition of endothelial cell growth was reverted by recombinant FGF-2.

Conclusion: Modulation of FGF-2 production by renal cell carcinoma with a blocking mAb produced a significant inhibition of endothelial cell growth.