Ahesion and protease activity are regulated by the laminin-derived peptide AG73, syndecan-1 and bintegrin in cell line derived from adenoid cystic carcinoma.

Author(s)

Elaine Cyreno Oliveira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2009-10-01

Examining board members

Ruy Gastaldoni Jaeger; Sergio Roberto Peres Line; Paulo Tambasco de Oliveira; Glaucia Maria Machado Santelli; Suzana Cantanhede Orsini Machado de Sousa

• Advisor: Ruy Gastaldoni Jaeger

Abstract

We studied induction of MMP activity by b1-laminin peptide AG73 in adenoid cystic carcinoma cell line (CAC2). Cells grown inside AG73-enriched laminin-111 exhibited pseudocystics spaces. MMP inhibitor decreased those spaces, suggesting MMPs action. Cells grown on AG73 showed a dose-dependent increase of MMP9 secretion. MMP9 siRNAi decreased remodeling in 3D culture. We searched for AG73 receptors regulating MMP9 activity. CAC2 grown on AG73 exhibited colocalization of syndecan-1 and b1 integrin. Syndecan-1 siRNA or siRNA b1 integrin showed reduction in adhesion to AG73 and in remodeling and protease activities. Double-knockdown explored syndecan-1 and 1 integrin cooperation and showed decrease in adhesion to AG73 and in MMP activity. Receptors characterization was made by affinity chromatography followed by mass spectrometry through AG73-affinity columns and showed putative receptors, like b1 and aV integrins. We suggest that AG73 peptide regulates adhesion and MMP secretion in CAC2 cells through syndecan-1 and b1 integrin. (AU)