Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX.
Fiche publication
Date publication
janvier 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie, Pr DAUCHEZ Manuel, Dr MONBOISSE Jean-Claude, Pr RAMONT Laurent, Dr BRASSART Bertrand, Dr OUDART Jean-Baptiste, Pr BAUD Stéphanie
Tous les auteurs :
Oudart JB, Brassart-Pasco S, Vautrin A, Sellier C, Machado C, Dupont-Deshorgue A, Brassart B, Baud S, Dauchez M, Monboisse JC, Harakat D, Maquart FX, Ramont L
Lien Pubmed
Résumé
During tumor invasion, tumor cells degrade the extracellular matrix. Basement membrane degradation is responsible for the production of peptides with anti-tumor properties. Type XIX collagen is associated with basement membranes in vascular, neuronal, mesenchymal and epithelial tissues. Previously, we demonstrated that the non-collagenous NC1, C-terminal, domain of collagen XIX [NC1(XIX)] inhibits the migration capacities of tumor cells and exerts a strong inhibition of tumor growth. Here, we demonstrate that plasmin, one of the most important enzyme involved in tumor invasion, was able to release a fragment of NC1(XIX), which retained the anti-tumor activity. Molecular modeling studies showed that NC1(XIX) and the anti-tumor fragment released by plasmin (F4) adopted locally the same type I beta-turn conformation. This suggests that the anti-tumor effect is conformation-dependent. This study demonstrates that collagen XIX is a novel proteolytic substrate for plasmin. Such release may constitute a defense of the organism against tumor invasion.
Référence
Oncotarget. 2015 Jan 21.