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The fact that elastin peptides, the degradation products of the extracellular matrix protein elastin, are chemotactic for numerous cell types, promote cell cycle progression and induce release of proteolytic enzymes by stromal and cancer cells, strongly suggests that their presence in tissues could contribute to tumour progression. Thus, elastin peptides qualify as matrikines, i.e. peptides originating from the fragmentation of matrix proteins and presenting biological activities. After a brief description of their origin, the biological activities of these peptides are reviewed, emphasising their potential role in cancer. The nature of their receptor and the signalling events it controls are also discussed. Finally, the structural selectivity of the elastin complex receptor is presented, leading to the concept of elastokine (matrikine originating from elastin fragmentation) and morpho-elastokine, i.e. peptides presenting a conformation similar to that of bioactive elastin peptides and mimicking their effects.

Tumor progression may be controlled by various fragments derived from noncollagenous 1 (NC1) C-terminal domains of type IV collagen. We demonstrated previously that a peptide sequence from the NC1 domain of the alpha3(IV) collagen chain inhibits the in vitro expression of matrix metalloproteinases in human melanoma cells through RGD-independent binding to alpha(v)beta(3) integrin. In the present paper, we demonstrate that in a mouse melanoma model, the NC1 alpha3(IV)-(185-203) peptide inhibits in vivo tumor growth in a conformation-dependent manner. The decrease of tumor growth is the result of an inhibition of cell proliferation and a decrease of cell invasive properties by down-regulation of proteolytic cascades, mainly matrix metalloproteinases and the plasminogen activation system. A shorter peptide comprising the seven N-terminal residues 185-191 (CNYYSNS) shares the same inhibitory profile. The three-dimensional structures of the CNYYSNS and NC1 alpha3(IV)-(185-203) peptides show a beta-turn at the YSNS (188-191) sequence level, which is crucial for biological activity. As well, the homologous MNYYSNS heptapeptide keeps the beta-turn and the inhibitory activity. In contrast, the DNYYSNS heptapeptide, which does not form the beta-turn at the YSNS level, is devoid of inhibitory activity. Structural studies indicate a strong structure-function relationship of the peptides and point to the YSNS turn as necessary for biological activity. These peptides could act as potent and specific antitumor antagonists of alpha(v)beta(3) integrin in melanoma progression.

Elastic fibers are an important component of the extracellular matrix, providing elasticity and resilience to tissues that require the ability to deform repetitively and reversibly. Among the elastin-derived peptides, the Val-Gly-Val-Ala-Pro-Gly (VGVAPG) hexapeptide is known for its chemotactic activity and metalloproteinases upregulation properties. As other elastin-derived peptides, having homologous similar sequences, do not exhibit any biological activity, the following question arises: Does the peptide-receptor interaction need a specific active conformation? Previous experimental studies including NMR and CD spectroscopies did not clearly identify the conformations adopted by the VGVAPG peptide in solution. However, structural predictions made on VGVAPG and related XGXXPG peptides suggested a folded beta-turn conformation. So we undertook a theoretical and experimental study of the VGVAPG peptide. The work presented here, which gives an overall structural description of VGVAPG behavior in water, also provides an additional insight into its structure-activity relationship. Both theoretical and experimental results suggest the existence of an ensemble of rather extended and folded conformations in solution. All the folded structures obtained exhibit a type VIII beta-turn spanning the GVAP sequence. In the lack of any structural information concerning the elastin receptor, these results suggest that such a conformation could be relevant for the peptide-receptor interaction and thus for biological activity., (Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004)