Vasohibin-1 Expression in Endothelium of Tumor Blood Vessels Regulates Angiogenesis
AUTOR(ES)
Hosaka, Tomoko
FONTE
American Society for Investigative Pathology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2708828Documentos Relacionados
- Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis
- Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors
- Vasohibin: the feedback on a new inhibitor of angiogenesis
- Vasohibin-1, a Negative Feedback Regulator of Angiogenesis, Ameliorates Renal Alterations in a Mouse Model of Diabetic Nephropathy
- Expression of hyaluronidase by tumor cells induces angiogenesis in vivo.