Malignancy-related 67 kDa laminin receptor in adenoid cystic carcinoma.: Effect on migration and β-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 beta 1 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 get (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 P-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 P-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 P-catenin expression, and migratory activity of CAC2 cells. (C) 2006 Elsevier Ltd. All rights reserved.