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

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.

[1]  M. Brandi,et al.  Inhibition of angiogenic activity of renal carcinoma by an antisense oligonucleotide targeting fibroblast growth factor-2. , 2005, Anticancer research.

[2]  M. Brandi,et al.  Isolation and characterization of a new cell line from a renal carcinoma bone metastasis. , 2004, Anticancer research.

[3]  H. Kuhn,et al.  Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines. , 2004, Lung cancer.

[4]  D. Ribatti,et al.  Bone Marrow Angiogenesis and Plasma Cell Angiogenic and Invasive Potential in Patients with Active Multiple Myeloma , 2002, Acta Haematologica.

[5]  A. Tarnawski,et al.  Inhibition of human colon cancer cell growth by antisense oligodeoxynucleotides targeted at basic fibroblast growth factor , 2001, Alimentary pharmacology & therapeutics.

[6]  A. Bikfalvi,et al.  Inhibition of fibroblast growth factor/fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms. , 2001, Cancer research.

[7]  A. El‐Naggar,et al.  Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. , 2001, The American journal of pathology.

[8]  Kozo Nakamura,et al.  Fibroblast Growth Factor (FGF)-2 Directly Stimulates Mature Osteoclast Function through Activation of FGF Receptor 1 and p42/p44 MAP Kinase* , 2000, The Journal of Biological Chemistry.

[9]  M. Nugent,et al.  Fibroblast growth factor-2. , 2000, The international journal of biochemistry & cell biology.

[10]  T. Sugimura,et al.  Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. , 1999, Biochemical and biophysical research communications.

[11]  D. Becker,et al.  Antisense targeting of basic fibroblast growth factor and dibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth , 1997, Nature Medicine.

[12]  R. Morrison.  Suppression of basic fibroblast growth factor expression by antisense oligodeoxynucleotides inhibits the growth of transformed human astrocytes. , 1991, The Journal of biological chemistry.

[13]  M. Brandi,et al.  Cloned endothelial cells from fetal bovine bone. , 1989, Proceedings of the National Academy of Sciences of the United States of America.