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.
Highlights
After transformation, tumor cells acquire accelerated proliferative capacity and spread to other locations
elastinderived peptides (EDPs)-dependent cell proliferation is mediated through VGVAPG-derived peptides; this sequence is repeated several times in tropoelastin, which binds to an elastin receptor with lectin-like properties known as elastin receptor complex (ERC) (S-galactosidase/neuraminidase-1/cathepsin A protective protein)
To confirm that in vivo tumor growth is directly mediated by VG-6 and AG-9, that is, that EDPs do not signal via other extracellular matrix (ECM) components, we evaluated their pro-proliferative abilities in B16-F1, SK-MEL-28, HT1080 and HT-29 cells
Summary
Tumor cells acquire accelerated proliferative capacity and spread to other locations. Elastin proteolysis by elastase-type proteinases (metallo, serine and cysteine families) is linked to the genesis of several diseases affecting elastin-rich organs [3, 4] This degradation is known to unmask cryptic sites within the ECM and to release matrikines, termed elastinderived peptides (EDPs) [5, 6]. These EDPs display a wide range of biological activities, influencing cell migration [7, 8], differentiation [9], proliferation, chemotaxis [10, 11], survival, tumor progression [12,13,14], angiogenesis [15], aneurysm formation and atherogenesis [16]. Lactose-preincubated cells are insensitive to EDPstimulation, resulting in a lack of cell proliferation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
