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 B16F10
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.