An essential role for decorin in bladder cancer invasiveness

EMBO Molecular Medicine

Mohamed El Behi¹  Sophie Krumeich¹  Catalina Lodillinsky⁶  Aurélie Kamoun¹  Lorenzo Tibaldi¹  Gaël Sugano¹  Aurélien De Reynies²  Elodie Chapeaublanc¹  Agnès Laplanche³  Thierry Lebret⁴  Yves Allory⁵  François Radvanyi¹  Olivier Lantz¹  Ana María Eiján⁶  Isabelle Bernard-Pierrot¹ 

[1] Institut Curie Research Center, Paris, France;Ligue Nationale Contre le Cancer, Cartes d'Identité des Tumeurs program, Paris, France;Département de Biostatistique et d'Epidémiologie, Institut de Cancérologie Gustave Roussy, Villejuif, France;Service d'Urologie, Hôpital Foch, Suresnes, France;AP-HP, Groupe Hospitalier Henri Mondor, Département de Pathologie, Créteil, France;CONICET researcher at Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina

关键词: angiogenesis;    bladder carcinoma;    decorin;    tumour immunity;    tumour microenvironment;   

DOI  :  10.1002/emmm.201302655

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.