Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas.
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.
Caudroy
Stephanie
S
Inserm UMRS 514, IFR53, CHU Maison-Blanche, Reims, France.
Cucherousset
Joel
J
Lorenzato
Marianne
M
Zahm
Jean-Marie
JM
Martinella-Catusse
Corinne
C
Polette
Myriam
M
Birembaut
Philippe
P
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
D001324:Autoantigens; D024141:Collagen Type IV; D039302:Integrin alphaVbeta3; C057112:type IV collagen alpha3 chain; D003094:Collagen