title: Laminin-111 derived peptides AG73 and C16 regulate invadopodia activity of a human adenoid cystic carcinoma cell line.
abstract: Adenoid cystic carcinoma is a frequently occurring malignant salivary gland neoplasm with high level of recurrence and distant metastasis long time after treatment. Metastatic tumor cells that actively migrate and invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM) barriers. Invadopodia are actin-rich membrane protrusions that localize enzymes required for ECM degradation. Breakdown of ECM macromolecules releases fragments and bioactive peptides. We have already demonstrated that laminin-111 and its derived peptides regulate migration, invasion and protease activity of adenocarcinoma cells. Here we addressed the role of laminin-111 peptides AG73 and C16 in invadopodia activity of cells (CAC2) derived from human adenoid cystic carcinoma. CAC2 cells were treated by AG73 and C16, and subjected to fluorescent gelatin substrate degradation assay. In this assay invadopodia activity areas appear as black dots in a fluorescent background. Both peptides significantly increased invadopodia formation and activity compared to controls. We analyzed putative receptors and signaling pathways related to peptide effects. β1 integrin silencing by siRNA decreased AG73- and C16-induced invadopodia. Furthermore inhibition of Rac1 and ERK signaling pathways decreased both C16- and AG73-related invadopodia activities. We propose that laminin-111 peptides AG73 and C16 increase invadopodia activity in CAC2 cells through β1 integrin. Rac1 and ERK1/2 signaling pathways would transduce signals generated by both peptides.
authors.affiliation: Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
authors.forename: Camila F
authors.initials: CF
authors.lastname: Nascimento
authors.forename: Adriane S
authors.initials: AS
authors.lastname: de Siqueira
authors.forename: João J V
authors.initials: JJ
authors.lastname: Pinheiro
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Freitas
authors.forename: Ruy G
authors.initials: RG
authors.lastname: Jaeger
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000473:pathology*; D022081:Cell Surface Extensions / Q000187:drug effects*; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D007797:Laminin; D010455:Peptides