title: Downregulation of vasohibin-2, a novel angiogenesis regulator, suppresses tumor growth by inhibiting angiogenesis in endometrial cancer cells.
abstract: The vasohibin-2 (VASH2) gene was originally found to be expressed in infiltrating mononuclear cells of a mouse model of hypoxia-induced subcutaneous angiogenesis. These cells are mobilized from bone marrow to promote angiogenesis. Recently, VASH2 has been demonstrated to be expressed in several types of cancer in which it promotes tumor development through angiogenesis. However, its role in endometrial cancer remains unknown. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), we found that VASH2 was overexpressed in several human endometrial cancer cell lines, including the HEC50B cell line, which we used to further examine the role of VASH2. Although knockdown of VASH2 with stable transfection of shRNA had little effect on the proliferation of HEC50B cells in vitro, knockdown in an in vivo murine xenograft model inhibited tumor growth by decreasing tumor angiogenesis. In addition, the supernatant from HEC50B cells that expressed VASH2 significantly promoted the proliferation of human umbilical vein endothelial cells. By contrast, knockdown of VASH2 significantly attenuated the proliferative effect. These results indicate that VASH2 contributes to the development of endometrial cancer by promoting angiogenesis through a paracrine mode of action. Consequently, VASH2 may be considered to be a novel molecular target for endometrial cancer therapy.
authors: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498; ; Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ward, Sendai 980-8575,  Japan.
authors: Takahiro
authors: T
authors: Koyanagi
authors: Yasushi
authors: Y
authors: Saga
authors: Yoshifumi
authors: Y
authors: Takahashi
authors: Yasuhiro
authors: Y
authors: Suzuki
authors: Mitsuaki
authors: M
authors: Suzuki
authors: Yasufumi
authors: Y
authors: Sato
keywords: endometrial cancer; endothelial cells; molecular-targeted therapy; tumor angiogenesis; vasohibin-2