| First Author | Hosaka T | Year | 2009 |
| Journal | Am J Pathol | Volume | 175 |
| Issue | 1 | Pages | 430-9 |
| PubMed ID | 19498005 | Mgi Jnum | J:150056 |
| Mgi Id | MGI:3849630 | Doi | 10.2353/ajpath.2009.080788 |
| Citation | Hosaka T, et al. (2009) Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis. Am J Pathol 175(1):430-9 |
| abstractText | 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 1alpha/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. |
