Cadherin Expression and Progression of Squamous Cell Carcinomas of the Oral Cavity

Abstract

Cell-cell adhesion plays fundamental and dynamic roles in the development and maintenance of multi-cellular organisms. Epithelial sheet is a typical structure and composed of cells that work together and separate from a lumen or space from underlying tissue. It lines most internal surfaces, including gastrointestinal tract and kidney tubes, and external layer of the epithelium as the epidermis of skin. The oral cavity is covered with stratified squamous cell epithelium in which keratinizing epithelial cells strongly connect with each other and differentiate from basal cells at the bottom to keratinized surface cells. Epithelial cells are connected together by junctional complexes that have distinct order with respect to their ultra-structures; zonula occludens (tight junctions), gap junctions, zonula adherens (adherence junctions) and macula adherens (desmosomes). Adherence junctions in epithelial sheet are belt like junctions and composed of cadherins that bind with proteins at the cytoplasmic domain. In other cell types, adherence junctions display different morphology; spotty and discontinuous in fibroblastic cells and punctate in the synaptic junctions. Desmosome is a spot-like junction associated with desmosomal cadherins (desmogleins and desmocollins) and tightly associated with adjacent cell membranes compared to adherence junctions. Stratified squamous epithelial cells express large amount of cadherins and well organize adherence junctions and desmosomes. Disruption of desmosomes by autoantibodies against desmoglein causes pemphigus that are multiple and bullous diseases in the skin and oral mucosa. Cadherins are most characterized cell-cell adhesion molecules and implicated in the development and progression of carcinomas of the epithelial origin. In this chapter, we overview the regulation and role of cadherins in the pathology of oral squamous cell carcinomas (OSCCs).