Expression and functional significance of vascular endothelial growth factor receptors in human tumor cells

• Published in: Laboratory investigation Vol. 79; no. 12; p. 1573
• Main Authors: Herold-Mende, C, Steiner, H H, Andl, T, Riede, D, Buttler, A, Reisser, C, Fusenig, N E, Mueller, M M
• Format: Journal Article
• Language: English
• Published: United States 01-12-1999
• Subjects: Base Sequence; Cell Division; Cell Movement; Culture Media, Conditioned; DNA Primers; Glioma - metabolism; Glioma - pathology; Humans; Melanoma - metabolism; Melanoma - pathology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Cells, Cultured; Vascular Endothelial Growth Factor Receptor-1
• ISSN: 0023-6837

Vascular endothelial growth factor (VEGF) is one of the key factors in tumor neoangiogenesis, acting through its receptors KDR (VEGFR-2) and fit-1 (VEGFR-1) expressed on endothelial cells. Our data demonstrate that VEGFR-1 and to a lesser extent VEGFR-2 are expressed in a number of human tumor tissues and derived cells in culture. VEGFR-1 protein is expressed in 26 of 42 glioma tissues, 22 of which show a coexpression of VEGFR-1 with VEGFR-2; 1 glioma tissue expresses exclusively VEGFR-2. In the derived glioma cell cultures, we found VEGFR-1 mRNA expression in 6 of 11 cultures, with one coexpressing VEGFR-1 and VEGFR-2. Of four established glioma cell lines, two expressed VEGFR-1. In addition VEGFR-1 protein expression was demonstrated in 30 of 37 tumor tissues of squamous cell carcinomas of the head and neck, with VEGFR-2 coexpression in 15 tissues and an expression of VEGFR-2 alone in 1 tissue. Derived tumor cell cultures showed mRNA expression of VEGFR-1 alone in seven of seven cases. Established melanoma cell lines expressed VEGFR-1 mRNA in four of five lines, with VEGFR-2 coexpression in two lines. Concerning the functional significance of VEGF receptor expression, VEGF treatment of VEGFR-1-expressing tumor cells induced the inhibition of cell proliferation by 25 to 55% and the inhibition of tumor cell migration by 29 to 55%. Thus our data indicate that the coexpression of VEGF and VEGFR-1 in tumor cells could have an inhibitory effect on tumor cell proliferation and migration, a mechanism possibly induced as a response to a deficiency in nutrient and oxygen supply.