Structural characterization and pro-tumor properties of a highly conserved matrikine.

Fiche publication

Date publication

avril 2018

Journal

Oncotarget

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BELJEBBAR Abdelilah , Dr BRASSART-PASCO Sylvie , Dr NUZILLARD Jean-Marc , Pr RAMONT Laurent , Dr BRASSART Bertrand , Dr BERQUAND Alexandre

Tous les auteurs :
Da Silva J, Lameiras P, Beljebbar A, Berquand A, Villemin M, Ramont L, Dukic S, Nuzillard JM, Molinari M, Gautier M, Brassart-Pasco S, Brassart B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29707150

Résumé

Elastin-derived peptides (EDPs) exert protumor activities by increasing tumor growth, migration and invasion. A number of studies have highlighted the potential of VGVAPG consensus sequence-derived elastin-like polypeptides whose physicochemical properties and biocompatibility are particularly suitable for applications, such as drug delivery and tissue engineering. However, among the EDPs, the influence of elastin-derived nonapeptides (xGxPGxGxG consensus sequence) remains unknown. Here, we show that the AGVPGLGVG elastin peptide (AG-9) present in domain-26 of tropoelastin is more conserved than the VGVAPG elastin peptide (VG-6) from domain-24 in mammals. The results demonstrate that the structural features of AG-9 and VG-6 peptides are similar. CD, NMR and FTIR spectroscopies show that AG-9 and VG-6 present the same conformation, which includes a mixture of random coils and β-turn structures. On the other hand, the supraorganization differs between peptides, as demonstrated by AFM. The VG-6 peptide gathers in spots, whereas the AG-9 peptide aggregates into short amyloid-like fibrils. An study showed that AG-9 peptides promote tumor progression to a greater extent than do VG-6 peptides. These results were confirmed by studies such as 2D and 3D proliferation assays, migration assays, adhesion assays, proteinase secretion studies and pseudotube formation assays to investigate angiogenesis. Our findings suggest the possibility that the AG-9 peptide present in patient sera may dramatically influence cancer progression and could be used in the design of new, innovative antitumor therapies.