Malignancy-related 67kDa laminin receptor in adenoid cystic carcinoma. Effect on migration and beta-catenin expression.
Adenoid cystic carcinoma is a malignant salivary gland neoplasm with recurrence and metastasis. We studied the expression of a malignancy-related non-integrin laminin receptor, the 67LR, in this neoplasm. Immunohistochemistry showed 67LR in adenoid cystic carcinoma. This receptor binds a sequence of laminin beta1 chain, the YIGSR peptide. We studied the effect of 67LR and YIGSR in cells (CAC2) from adenoid cystic carcinoma. Three-dimensional cultures of cells embedded into either laminin-111 gel (controls) or YIGSR-enriched laminin-111 (treated) were prepared and studied by light microscopy. CAC2 cells treated with YIGSR appeared fibroblast-like, while control cells were epithelioid. Blockage of 67LR by antibody abolished YIGSR effect in three-dimensional cultures. We analysed the relevance of 67LR and YIGSR on beta-catenin expression in CAC2 cells. Immunofluorescence and immunoblot showed that YIGSR decreased beta-catenin, while blockage of 67LR restored the presence of this molecule. The 67LR and YIGSR induced fibroblast-like morphology in CAC2 cells, with disruption of cell-cell contacts and decrease of beta-catenin. These features resemble epithelial-mesenchymal transition (EMT). EMT also increases cell migration. In monolayer assays YIGSR increased migration of CAC2 cells. We conclude that 67LR and YIGSR are involved in epithelial-mesenchymal transition, modulation of beta-catenin expression, and migratory activity of CAC2 cells.
Morais Freitas
Vanessa
V
Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Nogueira da Gama de Souza
Letícia
L
Cyreno Oliveira
Elaine
E
Furuse
Cristiane
C
Cavalcanti de Araújo
Vera
V
Gastaldoni Jaeger
Ruy
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D017474:Receptors, Laminin / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D007797:Laminin; D009363:Neoplasm Proteins; D009842:Oligopeptides; D017474:Receptors, Laminin; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine