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

// Jordan Da Silva 1 , Pedro Lameiras 2 , Abdelilah Beljebbar 1 , Alexandre Berquand 3 , Matthieu Villemin 1 , Laurent Ramont 1, 4 , Sylvain Dukic 1 , Jean-Marc Nuzillard 2 , Michael Molinari 3 , Mathieu Gautier 5 , Sylvie Brassart-Pasco 1 and Bertrand Brassart 1 1 UMR CNRS/URCA 7369 MEDyC, Universite de Reims Champagne Ardenne, UFR Medecine, 51095 Reims, France 2 ICMR, CNRS UMR 7312, UFR de Pharmacie, Universite de Reims Champagne-Ardenne, 51096 Reims, France 3 Laboratoire de Recherche en Nanosciences, LRN-EA4682, Universite de Reims Champagne-Ardenne, 51100 Reims, France 4 CHU de Reims, Laboratoire Central de Biochimie, 51092 Reims, France 5 Laboratoire de Physiologie Cellulaire et Moleculaire, LPCM - EA4667, Universite de Picardie Jules Verne, UFR Sciences, F-80039 Amiens, France Correspondence to: Bertrand Brassart, email: bertrand.brassart@univ-reims.fr Keywords: AGVPGLGVG; VGVAPG; elastin; cancer; structure-function Received: November 16, 2017     Accepted: February 25, 2018     Published: April 03, 2018 ABSTRACT 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 in vivo 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 in vivo study showed that AG-9 peptides promote tumor progression to a greater extent than do VG-6 peptides. These results were confirmed by in vitro 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.