In vitro effects of SIKVAV retro and retro-enantio analogues on tumor metastatic events

The SIKVAV peptide, located on the long arm of the laminin alpha1 chain, promotes cell adhesion, invasion and migration of tumor and endothelial cells, resulting in tumor growth, angiogenesis and metastasis. In this paper, we report the synthesis of the SIKVAV peptide and its retro (reverse L-amino acid order) and retro-enantio (reverse D-amino acid order) analogues and their effect on three critical steps in the metastatic process: cell-extracellular matrix protein (ECM) adhesion, cell migration and homotypic cell adhesion, using B 161710 melanoma cells. Results show that all peptides compete with laminin-1 cell attachment, but only SIKVAV induces peptide-cell adhesion. Retro analogue, but not retro-enantio, inhibits cell adhesion to SIKVAV, indicating that retro peptide recognizes the SIKVAV receptors while retro-enantio does not. Retro-enantio peptide is able to inhibit cell migration, by contrast of the SIKVAV chemoattractant activity. All three peptides reduce the homotypic cell adhesion in a dose-dependent manner, but retro-enantio sequence is the most effective reaching a 35% inhibition of controls at the higher concentration. These findings suggest that that both analogues of SIKVAV peptide, especially retro-enantio, may be considered as potential antimetastatic agents. (C) 2004 Published by Elsevier Inc.