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.
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Authors | Jean-Baptiste Oudart, Sylvie Brassart-Pasco, Alexia Vautrin, Christèle Sellier, Carine Machado, Aurelie Dupont-Deshorgue, Bertrand Brassart, S Baud, Manuel Dauchez, Jean-Claude Monboisse, Dominique Harakat, François-Xavier Maquart, Laurent Ramont |
Journal | Oncotarget
(Oncotarget)
Vol. 6
Issue 6
Pg. 3656-68
(Feb 28 2015)
ISSN: 1949-2553 [Electronic] United States |
PMID | 25668817
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Peptides
- Collagen
- Fibrinolysin
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Topics |
- Amino Acid Sequence
- Animals
- Cell Culture Techniques
- Cell Line, Tumor
- Chromatography, High Pressure Liquid
(methods)
- Collagen
(chemistry, metabolism)
- Fibrinolysin
(metabolism)
- Humans
- Melanoma
(chemistry, metabolism, pathology)
- Mice, Inbred C57BL
- Molecular Dynamics Simulation
- Molecular Sequence Data
- Neoplasm Invasiveness
- Neoplasms
(chemistry, metabolism, pathology)
- Peptides
(chemistry, metabolism)
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Proteolysis
- Transfection
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