title: The angiogenesis regulator vasohibin-1 inhibits ovarian cancer growth and peritoneal dissemination and prolongs host survival.
abstract: Vasohibin-1 (VASH1) is expressed in vascular endothelial cells stimulated by several angiogenic growth factors and displays autocrine activity to regulate angiogenesis via a negative feedback mechanism. In this study, we investigated the effect of VASH1 on ovarian cancer progression using VASH1-expressing ovarian cancer cells in vitro and in vivo. The growth ability of ovarian cancer cells engineered to express the VASH1 gene remained unchanged in vitro. However, we showed that VASH1 secretion by tumor cells inhibited the growth of human umbilical vein endothelial cells. Further, animal experiments showed that VASH1 expression inhibited tumor angiogenesis and growth. In a murine model of peritoneal dissemination of ovarian cancer cells, VASH1 inhibited peritoneal dissemination and ascites, resulting in significantly prolonged survival in mice. This indicates that VASH1 exerts an antitumor effect on ovarian cancer by inhibiting angiogenesis in the tumor environment. These findings suggest that a novel therapy based on VASH1 could be a useful therapeutic strategy for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Sizuo
authors.initials: S
authors.lastname: Machida
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, 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, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; C493181:VASH1 protein, human