title: Unique properties of 189 amino acid isoform of vascular endothelial growth factor in tumorigenesis.
abstract: The 189 amino acid isoform of vascular endothelial growth factor (VEGF189) has been shown to be more strongly associated with the cell membrane than other isoforms of human VEGF (VEGF121, VEGF165). To analyze the biological activities of these VEGF isoforms on tumor growth, we transfected human VEGF121, VEGF165 or VEGF189 cDNA into the human colon cancer cell line SW-480, and established several clones overexpressing these VEGF isoforms. The total amounts of VEGF protein in the culture supernatants of the VEGF189-transfectants were less than those of VEGF121 and VEGF165-transfectants. These transfectants showed no significant differences in growth in culture. Nevertheless, the rate of in vivo tumor growth of VEGF189-transfectants was faster than or equivalent to that of VEGF121-transfectants, while the VEGF165-transfectant showed the greatest enhancement of tumor growth. The protein levels of VEGF were markedly increased only in the VEGF189-transfectants cultured in the presence of heparin. The enhanced in vivo tumor growth of VEGF189-transfectants can be partly explained by the cell-associated features of VEGF189 molecules. The VEGF189 molecule, which is strongly bound to the cell surface, has unique properties and high potential in local angiogenesis and tumor growth in the cancer inductive microenvironment.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomii
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Nobuko
authors.initials: N
authors.lastname: Sawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Junichiro
authors.initials: J
authors.lastname: Kamochi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Osamura
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Norikazu
authors.initials: N
authors.lastname: Tamaoki
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006493:Heparin