Vasohibin‐1 expression inhibits advancement of ovarian cancer producing various angiogenic factors

• Published in: Cancer science 2016-05, Vol.107 (5), p.629-637
• Main Authors: Takahashi, Yoshifumi, Saga, Yasushi, Koyanagi, Takahiro, Takei, Yuji, Machida, Shizuo, Taneichi, Akiyo, Mizukami, Hiroaki, Sato, Yasufumi, Matsubara, Shigeki, Fujiwara, Hiroyuki
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - metabolism; Animals; Antitumor activity; Apoptosis; Ascites; Cancer therapies; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - therapeutic use; Cell Line, Tumor; Cell Proliferation; Chemotherapy; Endothelial cells; Endothelial Cells - metabolism; Female; Fibroblast growth factors; Humans; Kinases; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neovascularization, Pathologic; Original; Ovarian cancer; Ovarian Neoplasms - blood supply; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Pancreatic cancer; PDGF; Peritoneal Neoplasms - pathology; Peritoneal Neoplasms - secondary; Peritoneum; Peritoneum - pathology; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; Researchers; sFlt‐1; Signal Transduction; Studies; Survival Rate; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascularization; vasohibin‐1; Xenograft Model Antitumor Assays
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12911

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. In the current study, the expression of sFlt‐1 had no such effect on the high PDGF‐producing ovarian cancer cells (KOC‐2S) used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF‐producing cells (SHIN‐3), but also in high PDGF‐producing cells (KOC‐2S).