elastin and valyl-alanyl-prolyl-glycine

Melanomas containing more elastin are associated with higher stages of the disease. The interaction between elastin-derived peptides and melanoma cells appears to play an important role in the progression of melanomas. The effects of the elastin-derived peptides VGVAPG and VAPG have been investigated on the migration, invasion, adhesion and angiogenesis of human melanoma cells of different invasive potential. Elastin, tropoelastin and VGVAPG peptide were demonstrated at the invasion site of melanoma using histochemistry and immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG bind directly to 3 cell surface receptors: galectin-3, integrin alpha v beta 3 and elastin-binding protein. Our results suggest that the increased levels of elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they can increase the migration of melanoma cells and the expression of CXCR-4 and CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the expression of different adhesion molecules; (v) they increase the expression of the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these effects. Clinical and therapeutic aspects are also discussed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carrier Proteins; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Chemokine CXCL12; Chemotaxis; Disease Progression; Elastin; Flow Cytometry; Galectin 3; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Melanoma; Neoplasm Invasiveness; Neovascularization, Pathologic; Oligopeptides; Polymerase Chain Reaction; Receptors, CXCR4; Skin Neoplasms; Tropoelastin; Vascular Endothelial Growth Factor C

Thermolysin digests of human elastins were examined for reliable elastin peptide markers as determined by HPLC followed by amino acid sequencing of promising peaks. The tetrapeptide VAPG was found to occur in the early portion of the chromatogram in a highly reliable fashion. The peptide appears to be significantly amplified, when compared with the other peptides, in that it is derived from the hexapeptide repeat in elastin, VGVAPG, which repeats itself in two three-piece segments in the c-terminal portion of the tropoelastin molecule. VAPG serves as a highly reliable quantitative measure for human elastins, allowing sensitivities to less than a microgram. Thus, it is a significantly more accurate measure than other existing methods. Precision also appears to be enhanced because of the directness of the measurement. The use of VAPG as a quantitative marker for human elastin has clinical application in the study of elastin-based connective tissue diseases.

Topics: Adult; Amino Acid Sequence; Aorta; Biomarkers; Chromatography, High Pressure Liquid; Elastin; Exons; Female; Humans; Infant, Newborn; Male; Molecular Sequence Data; Oligopeptides; Peptide Fragments; Thermolysin