title: An essential role for decorin in bladder cancer invasiveness.
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.
authors.affiliation: Institut Curie Research Center, Paris, France; INSERM U932, Paris, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Behi
authors.forename: Sophie
authors.initials: S
authors.lastname: Krumeich
authors.forename: Catalina
authors.initials: C
authors.lastname: Lodillinsky
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kamoun
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tibaldi
authors.forename: Gaël
authors.initials: G
authors.lastname: Sugano
authors.forename: Aurélien
authors.initials: A
authors.lastname: De Reynies
authors.forename: Elodie
authors.initials: E
authors.lastname: Chapeaublanc
authors.forename: Agnès
authors.initials: A
authors.lastname: Laplanche
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Ana María
authors.initials: AM
authors.lastname: Eiján
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bernard-Pierrot
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D058575:Decorin; D034741:RNA, Small Interfering; C499308:Rag2 protein, mouse
keywords: angiogenesis; bladder carcinoma; decorin; tumour immunity; tumour microenvironment