Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells
Department of Cancer Biology
Basement Membrane; Cadherins; Calcium; Cell Adhesion; Cell Aggregation; Cell Movement; Collagen; Colonic Neoplasms; Cytoskeletal Proteins; Extracellular Matrix; Humans; Laminin; Neoplasm Invasiveness; Stromal Cells; Transfection; Tumor Cells, Cultured; alpha Catenin
BACKGROUND: The clinical behavior of colorectal cancer depends on its ability to invade and metastasize. Metastatic cells must dissociate from other cells and invade through basement membrane and stroma. Cell-cell adhesion in epithelial cells is mediated by the cell surface protein E-cadherin in association with alpha- and beta-catenin, which link E-cadherin to the cytoskeleton. Decreased cell-cell adhesion and increased motility on laminin have been correlated with more poorly differentiated and aggressive carcinomas.
METHODS: In this study, the RKO cell line, previously shown by us to lack E-cadherin expression, was transfected with the complementary DNA for E-cadherin. The transfectants were selected for high levels of surface expression by sequential FACS and examined in functional assays.
RESULTS: In comparison to control transfectants, the E-cadherin transfectants exhibited a more epithelial-like morphology, a 30% increase in Ca(2+)-dependent cell-cell aggregation, and a markedly reduced motility on the matrix proteins, collagen I and laminin.
CONCLUSIONS: These data demonstrate that correction of a defect in the cadherin/catenin cell-cell adhesion complex, often found in poorly differentiated and highly invasive tumors, facilitates increased cell-cell adhesion and retards tumor cell migration on basement membrane and stromal proteins.
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Citation: Ann Surg Oncol. 1995 Sep;2(5):378-85.
Breen, Ellen C.; Steele, Glenn D. Jr.; and Mercurio, Arthur M., "Role of the E-cadherin/alpha-catenin complex in modulating cell-cell and cell-matrix adhesive properties of invasive colon carcinoma cells" (1995). Cancer Biology Publications and Presentations. Paper 133.