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Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
Published on: March 26, 2018
Malignancy-related 67kDa laminin receptor in adenoid cystic carcinoma. Effect on migration and beta-catenin
Vanessa Morais Freitas1, Letícia Nogueira da Gama de Souza, Elaine Cyreno Oliveira
1Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Abstract:
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.
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