N-cadherin in Oral Squamous Cell Carcinoma

Abstract

Cadherins are a family of cell-cell adhesion molecules which can modulate phenotype and morphogenesis in a variety of tissues. Oral squamous cell carcinoma (OSCC) expresses the epithelial type cadherin (E-cadherin) in the intercellular junction. Histologically, two types of tumor cell migration can be observed in OSCC; the collective cell migration and the individual cell migration. In the former, large tumor nests maintain E-cadherin-mediated cell-cell contact and invade into surrounding connective tissue. The latter shows migration of isolated cells or small tumor nests. We immunohistochemically investigated the localization of cadherin in OSCC. E-cadherin expression was noted in all samples of OSCC irrespective of the histological differentiation of tumors. N-cadherin was expressed in 50% of poorly differentiated OSCC, and localized in cord-like tumor nests at the advancing front, where the cadherin subtype of tumor cells switched from E-cadherin to N-cadherin (the neural type cadherin). This finding suggested the epithelialmesenchymal transition (EMT), a phenomenon observed in the tissue morphogenesis during development, occurred in human OSCC tissue. Next, we studied roles of N-cadherin in tumor progression by in vitro assays using an E-cadherin(-)/Ncadherin(+) OSCC cell line. The cell line showed weak cell-cell contacts in the monolayer culture, and showed a high migration property by the Boyden chamber assay. In the suspension culture, however, they formed dense cell aggregates mediated by N-cadherin, and escaped from anoikis (apoptosis induced by loss of anchorage). Taken together, N-cadherin would be involved in the progression of OSCC via the enhanced migration and the survival in anchorage-deficient condition.