These authors contributed equally to this work.
An essential role for decorin in bladder cancer invasiveness
Version of Record online: 20 OCT 2013
© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 12, pages 1835–1851, December 2013
How to Cite
El Behi, M., Krumeich, S., Lodillinsky, C., Kamoun, A., Tibaldi, L., Sugano, G., De Reynies, A., Chapeaublanc, E., Laplanche, A., Lebret, T., Allory, Y., Radvanyi, F., Lantz, O., Eiján, A. M., Bernard-Pierrot, I. and Théry, C. (2013), An essential role for decorin in bladder cancer invasiveness. EMBO Mol Med, 5: 1835–1851. doi: 10.1002/emmm.201302655
- Issue online: 2 DEC 2013
- Version of Record online: 20 OCT 2013
- Manuscript Accepted: 6 SEP 2013
- Manuscript Revised: 2 SEP 2013
- Manuscript Received: 19 FEB 2013
- INSERM, Institut Curie and by grants from Fondation de France (to CT), INCa (INCA_5975 to CT, OL and FR), La Ligue Nationale Contre le Cancer (FR: équipe labellisée; OL: équipe labellisée), and the program “Carte d'Identité des Tumeurs”, initiated, developed
- Ligue Nationale Contre le Cancer
- bladder carcinoma;
- tumour immunity;
- tumour microenvironment
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.