Almiñana Núria, Grau-Oliete M Rosa, Reig Francesca, Rivera-Fillat M Pilar
Department of Peptide and Protein Chemistry, Institute for Chemical and Environmental Research, CSIC, 08034 Barcelona, Spain.
Peptides. 2004 Feb;25(2):251-9. doi: 10.1016/j.peptides.2003.12.016.
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.
位于层粘连蛋白α1链长臂上的SIKVAV肽可促进肿瘤细胞和内皮细胞的黏附、侵袭及迁移，从而导致肿瘤生长、血管生成和转移。在本文中，我们报道了SIKVAV肽及其反向（氨基酸顺序颠倒）和反向对映体（d型氨基酸顺序颠倒）类似物的合成，以及它们对转移过程中三个关键步骤的影响：细胞与细胞外基质蛋白（ECM）的黏附、细胞迁移和同型细胞黏附，实验采用B16F10黑色素瘤细胞。结果表明，所有肽都能与层粘连蛋白-1细胞附着竞争，但只有SIKVAV能诱导肽-细胞黏附。反向类似物而非反向对映体抑制细胞与SIKVAV的黏附，这表明反向肽能识别SIKVAV受体，而反向对映体则不能。与SIKVAV的趋化活性相反，反向对映体肽能够抑制细胞迁移。所有三种肽均以剂量依赖方式降低同型细胞黏附，但反向对映体序列最为有效，在较高浓度下可使对照的抑制率达到35%。这些发现表明，SIKVAV肽的两种类似物，尤其是反向对映体，可被视为潜在的抗转移剂。
