An essential role for decorin in bladder cancer invasiveness

Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours.Fil: El Behi, Mohamed. Institute Curie; Francia. Centre de Recherche de I; Francia. Inserm; FranciaFil: Krumeich, Sophie. Institute Curie; Francia. Inserm; FranciaFil: Lodillinsky, Catalina. Institute Curie; Francia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kamoun, Aurélie. Institute Curie; FranciaFil: Tibaldi, Lorenzo. Institute Curie; Francia. Inserm; FranciaFil: Sugano, Gaël. Institute Curie; Francia. Inserm; FranciaFil: de Reynies, Aurélien. Ligue Nationale Contre le Cancer; FranciaFil: Chapeaublanc, Elodie. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Laplanche, Agnès. Centre National de la Recherche Scientifique; Francia. Institut de Cancérologie Gustave Roussy; FranciaFil: Lebret, Thierry. Hôpital Foch. Service d; Francia. Université de Versailles; FranciaFil: Allory, Yves. Inserm; FranciaFil: Radvanyi, François. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lantz, Olivier. Institute Curie; Francia. Inserm; FranciaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernard Pierrot, Isabelle. Institute Curie; Francia. Centre National de la Recherche Scientifique; FranciaFil: Théery, Clotilde. Institute Curie; Francia. Inserm; Franci