title: Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors.
abstract: Vasohibin-1 (VASH1) is a negative feedback regulator of angiogenesis, the first to be discovered, and was identified in vascular endothelial growth factor (VEGF)-stimulated vascular endothelial cells. Vasohibin-1 inhibits abnormal vascularization induced by various angiogenic factors including fibroblast growth factor and platelet-derived growth factor (PDGF), in addition to VEGF. By focusing on this characteristic of VASH1, we investigated the antitumor effects of VASH1 expression on ovarian cancer cells that produce different angiogenic factors. By using a high VEGF-producing ovarian cancer cell line, SHIN-3, and a high PDGF-producing ovarian cancer cell line, KOC-2S, the cells were transfected with either a VEGF antagonist, soluble VEGF receptor-1 (sVEGFR-1, or sFlt-1), or VASH1 genes to establish their respective cellular expression. The characteristics of these transfectants were compared with controls. We previously reported that the expression of sFlt-1 inhibited tumor vascularization and growth of high VEGF-producing ovarian cancer cells, reduced peritoneal dissemination and ascites development, and prolonged the survival time of the host. However, in the current study, the expression of sFlt-1 had no such effect on the high PDGF-producing ovarian cancer cells used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells, but also in high PDGF-producing cells, reduced their peritoneal dissemination and ascites, and prolonged the survival time of the host. These results suggest that VASH1 is an effective treatment for ovarian cancer cells that produce different angiogenic factors.
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Taneichi
authors.affiliation: Division of Genetic Therapeutics, Center for Molecular Medicine, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary; D010537:Peritoneum / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D043925:Angiogenesis Inducing Agents; D018797:Cell Cycle Proteins; D010982:Platelet-Derived Growth Factor; C493181:VASH1 protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Angiogenesis; PDGF; ovarian cancer; sFlt-1; vasohibin-1