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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 antitumor 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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https://hal.univ-reims.fr/hal-03541824
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Submitted on : Tuesday, January 25, 2022 - 10:00:41 AM
Last modification on : Friday, February 25, 2022 - 11:17:27 AM
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Jean-Baptiste Oudart, Sylvie Brassart-Pasco, Alexia Vautrin, Christèle Sellier, Carine Machado, et al.. Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX. Oncotarget, Impact journals, 2015, 6 (6), pp.3656-3668. ⟨10.18632/oncotarget.2849⟩. ⟨hal-03541824⟩

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