title: Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX.
abstract: 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 β-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.
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors: Jean-Baptiste
authors: JB
authors: Oudart
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors: Sylvie
authors: S
authors: Brassart-Pasco
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors: Alexia
authors: A
authors: Vautrin
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors: Christèle
authors: C
authors: Sellier
authors: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR N°7312, Faculté de Pharmacie, Reims, France.
authors: Carine
authors: C
authors: Machado
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors: Aurelie
authors: A
authors: Dupont-Deshorgue
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors: Bertrand
authors: B
authors: Brassart
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|Plateau de Modélisation Moléculaire Multi-échelle, UFR Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, Reims, France.
authors: S
authors: S
authors: Baud
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|Plateau de Modélisation Moléculaire Multi-échelle, UFR Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, Reims, France.
authors: Manuel
authors: M
authors: Dauchez
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors: Jean-Claude
authors: JC
authors: Monboisse
authors: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR N°7312, Faculté de Pharmacie, Reims, France.
authors: Dominique
authors: D
authors: Harakat
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors: François-Xavier
authors: FX
authors: Maquart
authors: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors: Laurent
authors: L
authors: Ramont
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D014162:Transfection
chemical_list: D010455:Peptides; D003094:Collagen; D005341:Fibrinolysin