SIKVAV, a laminin α1-derived peptide, interacts with:: Integrins and increases protease activity of a human salivary gland adenoid cystic carcinoma cell, line through the ERK 1/2 signaling pathway

Adenoid cystic carcinoma is a frequently occurring malignant salivary gland neoplasm. We studied the induction of protease activity by the laminin-derived peptide, SIKVAV, in cells (CAC2) derived from this neoplasm. Laminin alpha 1 and matrix metalloproteinases (MMPs) 2 and 9 were immunolocalized in adenoid cystic carcinoma cells in vivo and in vitro. CAC2 cells cultured on SIKVAV showed a dose-dependent increase of MMP9 as detected by zymography and colocalization of alpha 3 and alpha 6 integrins. Small interfering RNA (siRNA) knockdown of integrin expression in CAC2 cells resulted in decreased adhesion to the peptide. SIKVAV affinity chromatography and immunoblot analysis showed that alpha 3, alpha 6, and beta 1 integrins; were eluted from the SIKVAV column, which was confirmed by mass spectrometry and a solid-phase binding, assay. Small interfering RNA experiments also showed that these integrins, through extracellular signal-regulated kinase (ERK) 1/2 signaling, regulate MMP secretion induced by SIKVAV in CAC2 cells. We propose that SIKVAV increases protease activity of a human salivary gland adenoid cystic carcinoma cell line through alpha 3 beta b and alpha 6 beta 1 integrins and the ERK 1/2 signaling pathway.