An essential role for decorin in bladder cancer invasiveness

• Published in: EMBO molecular medicine Vol. 5; no. 12; pp. 1835 - 1851
• Main Authors: El Behi, Mohamed, Krumeich, Sophie, Lodillinsky, Catalina, Kamoun, Aurélie, Tibaldi, Lorenzo, Sugano, Gaël, De Reynies, Aurélien, Chapeaublanc, Elodie, Laplanche, Agnès, Lebret, Thierry, Allory, Yves, Radvanyi, François, Lantz, Olivier, Eiján, Ana María, Bernard‐Pierrot, Isabelle, Théry, Clotilde
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2013; EMBO Press; Wiley Open Access; John Wiley and Sons; Springer Nature
• Subjects: Adaptive Immunity; Angiogenesis; Animal models; Animals; Antigens; Bladder cancer; bladder carcinoma; Cell Line, Tumor; Cell Movement; Cytokines - metabolism; Decorin; Decorin - antagonists & inhibitors; Decorin - genetics; Decorin - metabolism; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Experiments; Female; Humans; Immune response; Immune system; Invasiveness; Life Sciences; Lymphocytes; Male; Medical prognosis; Metastasis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovarian cancer; Research Article; RNA Interference; RNA, Small Interfering - metabolism; Software; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Therapeutic applications; Tumors; tumour immunity; tumour microenvironment; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urothelial carcinoma; bladder carcinoma; tumour microenvironment; tumour immunity; decorin; angiogenesis
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.1002/emmm.201302655

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. Graphical Abstract Only a small fraction of patients with non‐invasive bladder cancer respond well to therapy. This study shows that the adaptive immune system cannot control invasive bladder tumors, while Decorin is found critical for this cancer progression.