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A more recent version of this article appeared on July 1, 2007

Published online before print May 24, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.051264

Accepted for publication March 27, 2007.

Article

SIKVAV, a Laminin {alpha}1-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

Vanessa M. Freitas*, Vanessa F. Vilas-Boas*, Daniel C. Pimenta{dagger}, Vania Loureiro{ddagger}, Maria A. Juliano{sect}, Márcia R. Carvalho, João J.V. Pinheiro, Antonio C.M. Camargo{dagger}, Anselmo S. Moriscot*, Matthew P. Hoffman||, and Ruy G. Jaeger*@

From the Department of Cellular and Developmental Biology,* Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Center for Applied Toxinology,{dagger} Butantan Institute, São Paulo, Brazil; Universidade Metropolitana de Santos,{ddagger} Santos, São Paulo, Brazil; Department of Biophysics,{sect} Universidade Federal de São Paulo, São Paulo, Brazil; Department of Oral Pathology, School of Dentistry, University of Pará, Belém, Pará, Brazil; and National Institute of Dental and Craniofacial Research,|| National Institutes of Health, Bethesda, Maryland

@ To whom correspondence should be addressed. E-mail: rgjaeger{at}usp.br.


  Abstract

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}1 and {alpha}6{beta}1 integrins and the ERK 1/2 signaling pathway.






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Copyright © 2007 by the American Society for Investigative Pathology.