Adhesion and protease activity in cell lines from human salivary gland tumors are regulated by the laminin-derived peptide AG73, syndecan-1 and beta 1 integrin


Autoria(s): GAMA-DE-SOUZA, Leticia N.; CYRENO-OLIVEIRA, Elaine; FREITAS, Vanessa M.; MELO, Edielle S.; VILAS-BOAS, Vanessa F.; MORISCOT, Anselmo S.; JAEGER, Ruy G.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2008

Resumo

We studied the induction of protease activity by the laminin alpha 1-derived peptide AG73 in cells from adenoid cystic carcinoma (CAC2) and myoepithelioma (M1), respectively a malignant and a benign salivary gland tumors. Laminin alpha 1 chain and MMP9 were immunolocalized in adenoid cystic carcinoma and myoepithelioma in vivo and in vitro. Cells grown inside AG73-enriched laminin-111 exhibited large spaces in the extracellular matrix, suggestive of remodeling. The broad spectrum MMP inhibitor GM6001 decreased spaces induced by AG73 in CAC2 and M I cells. This result strongly suggests that AG73-mediated matrix remodeling involves matrix metalloproteinases. CAC2 and M1 cells cultured on AG73 showed a dose-dependent increase of MMP9 secretion, as detected by zymography. Furthermore, siRNA silencing of MMP9 decreased remodeling in 3D cultures. We searched for AG73 receptors regulating MMP9 activity in our cell lines. CAC2 and M1 cells grown on AG73 exhibited colocalization of syndecan-1 and beta 1 integrin. siRNA knockdown of syndecan-1 expression in these cells resulted in decreased adhesion to AG73 and reduced protease and remodeling activity. We investigated syndecan-1 co-receptors in both cell lines. Silencing beta 1 integrin inhibited adhesion to AG73, matrix remodeling and protease activity. Double-knockdown experiments were carried out to further explore syndecan-1 and beta 1 integrin cooperation. CAC2 cells transfected with both syndecan-1 and beta 1 integrin siRNA oligos showed significant decrease in adhesion to AG73. Simultaneous silencing of receptors also induced a decrease in protease activity. Our results suggest that syndecan-1 and beta 1 integrin signaling downstream of AG73 regulate adhesion and MMP production by CAC2 and M1 cells. (c) 2008 Elsevier B.V./International Society of Matrix Biology. All rights reserved.

Identificador

MATRIX BIOLOGY, v.27, n.5, p.402-419, 2008

0945-053X

http://producao.usp.br/handle/BDPI/28623

10.1016/j.matbio.2008.02.007

http://dx.doi.org/10.1016/j.matbio.2008.02.007

Idioma(s)

eng

Publicador

ELSEVIER SCIENCE BV

Relação

Matrix Biology

Direitos

restrictedAccess

Copyright ELSEVIER SCIENCE BV

Palavras-Chave #salivary gland tumors #adenoid cystic carcinoma #myoepithelioma #extracellular matrix #laminin #matrix metalloproteinases #syndecan #integrins #ADENOID CYSTIC CARCINOMA #EPITHELIAL BRANCHING MORPHOGENESIS #NEOPLASTIC MYOEPITHELIAL CELLS #HOMOLOGOUS LOOP REGIONS #MUSCLE-SPECIFIC ACTIN #CHAIN G DOMAIN #ALPHA-1 CHAIN #BASEMENT-MEMBRANE #EXTRACELLULAR-MATRIX #SYNTHETIC PEPTIDES #Biochemistry & Molecular Biology #Cell Biology
Tipo

article

original article

publishedVersion