title: Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas.
abstract: The NC1 domain of alpha3 chain of type IV collagen, namely tumstatin, has been shown to display specific anti-angiogenic properties by inhibiting endothelial cells' proliferation and inducing their apoptosis via an interaction with alphavbeta3 integrin. Until now, the tumstatin anti-angiogenic effect has only been shown by in vitro studies or mouse xenograft experiments. In the present study, we examined the expression of tumstatin in relationship with tumor vascularization in 34 bronchopulmonary human carcinomas. We observed a clear association between tumstatin expression and tumor vascularization. Indeed, a strong expression of tumstatin in the tumor environment correlated with a mildly developed vascular network. In contrast, tumstatin was absent or poorly detected in highly vascularized tumors. Moreover, alphavbeta3 integrin and tumstatin colocalized in capillary endothelial cells, suggesting a potential interaction between these 2 molecules. Thus, our results plead in favor of an in vivo anti-angiogenic effect of tumstatin. This factor, largely expressed in well-differentiated lung carcinomas, could indeed reduce tumor vascularization and thereby limit tumor progression.
authors.affiliation: Inserm UMRS 514, IFR53, CHU Maison-Blanche, Reims, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Caudroy
authors.forename: Joel
authors.initials: J
authors.lastname: Cucherousset
authors.forename: Marianne
authors.initials: M
authors.lastname: Lorenzato
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Zahm
authors.forename: Corinne
authors.initials: C
authors.lastname: Martinella-Catusse
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism*; D001980:Bronchi / Q000098:blood supply / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism; D003094:Collagen; D024141:Collagen Type IV / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism*; D009389:Neovascularization, Pathologic
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D039302:Integrin alphaVbeta3; C057112:type IV collagen alpha3 chain; D003094:Collagen