Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR

• Published in: Journal of cancer research and clinical oncology 1999-11, Vol.125 (11), p.621-629
• Main Authors: GRAEVEN, U, FIEDLER, W, KARPINSKI, S, ERGÜN, S, KILIC, N, RODECK, U, SCHMIEGEL, W, HOSSFELD, D. K
• Format: Article
• Language: English
• Subjects: Antibody Specificity; Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; Culture Media, Conditioned - metabolism; DNA, Antisense - pharmacology; Endothelial Growth Factors - biosynthesis; Endothelial Growth Factors - genetics; Endothelial Growth Factors - metabolism; Endothelial Growth Factors - pharmacology; Enzyme-Linked Immunosorbent Assay; Host-tumor relations. Immunology. Biological markers; Humans; Immunohistochemistry; Lymphokines - biosynthesis; Lymphokines - genetics; Lymphokines - metabolism; Lymphokines - pharmacology; Medical sciences; Melanoma - metabolism; Proto-Oncogene Proteins - biosynthesis; Receptor Protein-Tyrosine Kinases - biosynthesis; Receptors, Growth Factor - biosynthesis; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Tumors; Urokinase-Type Plasminogen Activator - metabolism; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s004320050325

The expression patterns of vascular endothelial growth factor (VEGF) and its two receptors, flt-1 and KDR, were assessed in normal human melanocytes, transformed melanocytes expressing the simian virus 40 Tgene (SV40T), and melanoma cells derived from primary and metastatic lesions. Constitutive expression of VEGF, flt-1, and KDR mRNA and proteins was observed in the majority of primary and metastatic melanoma cell lines, and in SV40T-transformed melanocytes. VEGF expression in melanoma cell lines was further enhanced by exogenous growth factors including insulin and fetal calf serum. By contrast, neonatal melanocytes did not express VEGF or VEGF receptors and VEGF expression could not be induced by exogenous growth factors. Exogenous VEGF had no significant effects on melanoma cell proliferation or on production of a transcriptional target for VEGF, urokinase-type plasminogen activator. Down-regulation of VEGF expression in the metastatic melanoma cell line WM164 through transfection of a VEGF antisense construct similarly did not affect proliferation of the transfected cells in the presence or absence of exogenous VEGF. In summary, coexpression of VEGF and its receptors is a tumor-associated phenomenon in melanoma development. However VEGF production does not support autocrine proliferation of the melanoma cell lines tested.