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

Vascular endothelial growth factor (VEGF) is one of the key factors in tumo r neoangiogenesis, acting through its receptors KDR (VEGFR-2) and flt-1 (VE GFR-1) expressed on endothelial cells. Our data demonstrate that VEGFR-1 an d to a lesser extent VEGFR-2 are expressed in a number of human tumor tissu es and derived cells in culture. VEGFR-1 protein is expressed in 26 of 42 g lioma tissues, 22 of which show a coexpression of VEGFR-1 with VEGFR-2; 1 g lioma tissue expresses exclusively VEGFR-2. In the derived glioma cell cult ures, we found VEGFR-1 mRNA expression in 6 of 11 cultures, with one coexpr essing VEGFR-1 and VEGFR-2. Of four established glioma cell lines, two expr essed VEGFR-1. In addition VEGFR-1 protein expression was demonstrated in 3 0 of 37 tumor tissues of squamous cell carcinomas of the head and neck, wit h 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 alo ne 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. Conc erning the functional significance of VEGF receptor expression, VEGF treatm ent of VEGFR-1-expressing tumor cells induced the inhibition of cell prolif eration 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 tumo r cells could have an inhibitory effect on tumor cell proliferation and mig ration, a mechanism possibly induced as a response to a deficiency in nutri ent and oxygen supply.