Article

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

Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
American Journal Of Pathology (impact factor: 4.89). 08/2009; 175(1):430-9. DOI:10.2353/ajpath.2009.080788 pp.430-9
Source: PubMed

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 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.

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Keywords

adenoviral human vasohibin-1 gene
 
adenoviral human vasohibin-1 gene-treated mice
 
antitumor effect
 
apoptotic tumor cells
 
cancer cells
 
cisplatin's antitumor activity
 
conventional chemotherapy
 
endothelial cells
 
fibroblast growth factor-2 expression
 
immature blood vessels
 
Lewis lung carcinoma cells
 
mural cells
 
non-small cell lung carcinoma
 
pathological sections
 
remaining tumor vessels
 
sufficient exogenous vasohibin-1
 
tail vein injection
 
tumor angiogenesis
 
vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1
 
wild-type mice