title: Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis.
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.
authors.affiliation: Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hosaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Heishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Miyashita
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohta
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sonoda
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018827:Carcinoma, Lewis Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D042461:Vascular Endothelial Growth Factor A; C510089:Vash1 protein, mouse; D016222:Fibroblast Growth Factor 2; D002945:Cisplatin