Loss of E-cadherin is Associated with a Migratory Epithelial Phenotype

Objectives: E-cadherin is a homotypic adhesion molecule, critical for formation and maintenance of cell-cell contacts in epithelium. In carcinomas, loss of e-cadherin correlates with high tumour grade and poor prognosis. The aim of this study was to determine the relationship between e-cadherin expression and cell migration. Methods: Normal oral keratinocytes (NHK), a skin line (UP) and oral cancer cell lines (H103, H357, H413, H376) were analysed for e-cadherin mRNA by Northern blots and densitometry (arbritary units (AU)). Cell motility was measured over 4 hours by counting cells per high power field (hpf) which transmigrated through fibronectin coated transwell plates. Results: E-cadherin expression was high in NHK and those cell lines exhibiting an epithelioid growth pattern (NHK: 100 (5.4)AU, H103: 36.2 (5.5), UP: 43.2 (4.6)(mean (SD)), this was associated with a low migratory phenotype (NHK: 0.3 (0.7) cells/hpf, H103: 8.4 (2.5), UP: 9.9 (2.8)). H357 and H413 expressed an intermediate level of e-cadherin (11.1 (0.5) & 12.8 (1.4)AU respectively) and migration (28.6 (5.4), 32.9 (6.5)). H376, with a spindled phenotype showed low levels of e-cadherin (0.17), associated with a high migration (117.9 (22.3)). There was a close correlation between low e-cadherin expression and migration across all cells studied (R² = -0.85). Conclusions: This study confirms that loss of e-cadherin is associated with increased cell migration, and supports immunohistochemical studies that e-cadherin is associated with cancer progression. The correlation between e-cadherin mRNA and motility across a broad range emphasises the central role it has in controlling epithelial behaviour and therefore may be an important target in the prevention of cancer progression and metastasis.