Fiche publication
Date publication
juillet 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie
,
Dr SALESSE Stéphanie
,
Dr BRASSART Bertrand
Tous les auteurs :
Donet M, Brassart-Pasco S, Salesse S, Maquart FX, Brassart B
Lien Pubmed
Résumé
BACKGROUND: The elastin-derived peptides (EDPs) exert protumoural activities by potentiating the secretion of matrix metalloproteinases (MMP) and the plasminogen-plasmin activating system. In the present paper, we studied heat-shock protein 90 (Hsp90) involvement in this mechanism. METHODS: HT-1080 fibrosarcoma cell migration and invasion were studied in artificial wound assay and modified Boyden chamber assay, respectively. Heat-shock protein 90 was studied by western blot and immunofluorescence. Matrix metalloproteinase-2 and urokinase plasminogen activator (uPA) were studied by gelatin +/- plasminogen zymography and immunofluorescence. Heat-shock protein 90 partners were studied by immunoprecipitation. Messenger RNA expression was studied using real-time PCR. Small interfering RNAs were used to confirm the essential role of Hsp90. RESULTS: We showed that kappa-elastin and VGVAPG elastin hexapeptide stimulated Hsp90, pro-MMP-2 and uPA secretion within 6 h, whereas AGVPGLGVG and GRKRK peptides had no effect. No increase of mRNA level was observed. Heat-shock protein 90-specific inhibitors inhibit EDP-stimulated HT-1080 cell-invasive capacity and restrained EDP-stimulated pro-MMP-2 and uPA secretions. The inhibitory effect was reproduced by using Hsp90-blocking antibody or Hsp90 knockdown by siRNA. Heat-shock protein 90 interacted with and stabilised uPA and pro-MMP-2 in conditioned culture media of HT-1080 fibrosarcoma cells. CONCLUSIONS: Taken together, our results demonstrate that EDPs exert protumoural activities through an Hsp90-dependent mechanism involving pro-MMP-2 and uPA.
Référence
Br J Cancer. 2014 Jul 8;111(1):139-48