Research Papers:

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

Jordan Da silva, Pedro Lameiras, Abdelilah Beljebbar, Alexandre Berquand, Matthieu Villemin, Laurent Ramont, Sylvain Dukic, Jean-Marc Nuzillard, Michael Molinari, Mathieu Gautier, Sylvie Brassart-Pasco and Bertrand Brassart _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:17839-17857. https://doi.org/10.18632/oncotarget.24894

Metrics: PDF 1190 views  |   HTML 2362 views  |   ?  


Jordan Da Silva1, Pedro Lameiras2, Abdelilah Beljebbar1, Alexandre Berquand3, Matthieu Villemin1, Laurent Ramont1,4, Sylvain Dukic1, Jean-Marc Nuzillard2, Michael Molinari3, Mathieu Gautier5, Sylvie Brassart-Pasco1 and Bertrand Brassart1

1UMR CNRS/URCA 7369 MEDyC, Université de Reims Champagne Ardenne, UFR Médecine, 51095 Reims, France

2ICMR, CNRS UMR 7312, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51096 Reims, France

3Laboratoire de Recherche en Nanosciences, LRN-EA4682, Université de Reims Champagne-Ardenne, 51100 Reims, France

4CHU de Reims, Laboratoire Central de Biochimie, 51092 Reims, France

5Laboratoire de Physiologie Cellulaire et Moléculaire, LPCM - EA4667, Université de Picardie Jules Verne, UFR Sciences, F-80039 Amiens, France

Correspondence to:

Bertrand Brassart, email: [email protected]

Keywords: AGVPGLGVG; VGVAPG; elastin; cancer; structure-function

Received: November 16, 2017    Accepted: February 25, 2018    Published: April 03, 2018


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24894