title: SIKVAV, a laminin alpha1-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.
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 alpha1 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 alpha3 and alpha6 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 alpha3, alpha6, and beta1 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 alpha3beta1 and alpha6beta1 integrins and the ERK 1/2 signaling pathway.
authors.affiliation: Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Biologia Celular e do Desenvolvimento, Av Prof Lineu Prestes 1524, Ed Biomédicas 1, sala 405, São Paulo SP, Brazil.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Freitas
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Vilas-Boas
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pimenta
authors.forename: Vania
authors.initials: V
authors.lastname: Loureiro
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Carvalho
authors.forename: João J V
authors.initials: JJ
authors.lastname: Pinheiro
authors.forename: Antonio C M
authors.initials: AC
authors.lastname: Camargo
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hoffman
authors.forename: Ruy G
authors.initials: RG
authors.lastname: Jaeger
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism*; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D039503:Integrin alpha6; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D009842:Oligopeptides; C077583:seryl-isoleucyl-lysyl-valyl-alanyl-valinamide; C084098:laminin A; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9