Laminin-111 derived peptides AG73 and C16 regulate invadopodia activity of a human adenoid cystic carcinoma cell line

Autor(es)

Nascimento, Camila F. ^[1] ; de Siqueira, Adriane S. ^[1] ; Pinheiro, Joao J. V. ^{[1, 2]} ; Freitas, Vanessa M. ^[1] ; Jaeger, Ruy G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Cellular & Dev Biol, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil

^[2] Fed Univ Para, Dept Oral Pathol, Sch Dent, BR-66059 Belem, Para - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Cell Research; v. 317, n. 18, p. 2562-2572, NOV 1 2011.
• Citações Web of Science: 14

Resumo

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. beta 1 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 beta 1 integrin. Rac1 and ERK1/2 signaling pathways would transduce signals generated by both peptides. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 09/17336-6 - Peptídeos bioativos da laminina induzindo invadopódios em linhagem celular derivada de carcinoma epidermóide: estudo dinâmico por microscopia 4D
• Beneficiário: Adriane Sousa de Siqueira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 08/55848-6 - Papel de peptideos bioativos da laminina na atividade dos invadopodios em linhagem celular derivada de carcinoma adenoide cistico
• Beneficiário: Camila Nascimento Mantelli
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/57103-8 - Dinamica de formacao de invadopodios em linhagens tumorais tratadas por peptideos bioativos da laminina. estudo por microscopia 4d
• Beneficiário: Ruy Gastaldoni Jaeger
• Modalidade de apoio: Auxílio à Pesquisa - Regular