title: Expression and functional significance of vascular endothelial growth factor receptors in human tumor cells.
abstract: 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.
authors.affiliation: Department of Neurosurgery, University of Heidelberg, Germany. Christel_Herold-Mende@med.uni-heidelberg.de
authors.forename: C
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: H H
authors.initials: HH
authors.lastname: Steiner
authors.forename: T
authors.initials: T
authors.lastname: Andl
authors.forename: D
authors.initials: D
authors.lastname: Riede
authors.forename: A
authors.initials: A
authors.lastname: Buttler
authors.forename: C
authors.initials: C
authors.lastname: Reisser
authors.forename: N E
authors.initials: NE
authors.lastname: Fusenig
authors.forename: M M
authors.initials: MM
authors.lastname: Mueller
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement; D017077:Culture Media, Conditioned; D017931:DNA Primers; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1