AG-9, an Elastin-Derived Peptide, Increases In Vitro Oral Tongue Carcinoma Cell Invasion, through an Increase in MMP-2 Secretion and MT1-MMP Expression, in a RPSA-Dependent Manner.

Fiche publication


Date publication

décembre 2020

Journal

Biomolecules

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie, Dr BRASSART Bertrand, Pr BAUD Stéphanie


Tous les auteurs :
Bretaudeau C, Baud S, Dupont-Deshorgue A, Cousin R, Brassart B, Brassart-Pasco S

Résumé

Oral tongue squamous cell carcinoma is one of the most prevalent head and neck cancers. During tumor progression, elastin fragments are released in the tumor microenvironment. Among them, we previously identified a nonapeptide, AG-9, that stimulates melanoma progression in vivo in a mouse melanoma model. In the present paper, we studied AG-9 effect on tongue squamous cell carcinoma invasive properties. We demonstrated that AG-9 stimulates cell invasion in vitro in a modified Boyen chamber model. It increases MMP-2 secretion, analyzed by zymography and MT1-MMP expression, studied by Western blot. The stimulatory effect was mediated through Ribosomal Protein SA (RPSA) receptor binding as demonstrated by SiRNA experiments. The green tea-derived polyphenol, (-)-epigallocatechin-3-gallate (EGCG), was previously shown to bind RPSA. Molecular docking experiments were performed to compare the preferred areas of interaction of AG-9 and EGCG with RPSA and suggested overlapping areas. This was confirmed by competition assays. EGCG abolished AG-9-induced invasion, MMP-2 secretion, and MT1-MMP expression.

Mots clés

EGCG, MMP-2, elastin, ribosomal protein SA, tongue carcinoma

Référence

Biomolecules. 2020 Dec 30;11(1):