Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis

Tomoko Hosaka, Hiroshi Kimura, Takahiro Heishi, Yasuhiro Suzuki, Hiroki Miyashita, Hideki Ohta, Hikaru Sonoda, Takuya Moriya, Satoshi Suzuki, Takashi Kondo, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

In this study, we characterized the significance of the vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1 to tumors. In pathological sections of non-small cell lung carcinoma, vasohibin-1 was present in the endothelial cells of blood vessels of the tumor stroma, but not in the lymphatics. In cancer cells, the presence of vasohibin-1 was associated with hypoxia-inducible factor 1α/vascular endothelial growth factor and fibroblast growth factor-2 expression. We then examined the function of vasohibin-1 in the mouse by subcutaneously inoculating with Lewis lung carcinoma cells. Resultant tumors in vasohibin-1/ mice contained more immature blood vessels and fewer apoptotic tumor cells than tumors in wild-type mice. In wild-type mice that had been inoculated with Lewis lung carcinoma cells, tail vein injection of adenovirus containing the human vasohibin-1 gene inhibited tumor growth and tumor angiogenesis. Moreover, the remaining tumor vessels in adenoviral human vasohibin-1 gene-treated mice were small, round, and mature, surrounded by mural cells. The addition of adenoviral human vasohibin-1 gene to cisplatin treatment improved cisplatin"s antitumor activity in mice. These results suggest that endogenous vasohibin-1 is not only involved in tumor angiogenesis, but when sufficient exogenous vasohibin-1 is supplied, it blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy.

Original languageEnglish
Pages (from-to)430-439
Number of pages10
JournalAmerican Journal of Pathology
Volume175
Issue number1
DOIs
Publication statusPublished - 2009 Jul

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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