Loss of invasiveness in squamous cell carcinoma cells overexpressing desmosomal cadherins

The molecular and structural characteristics of intercellular adhesion were investigated in a squamous cell carcinoma (SCCA) cell line, originally der ived from an oral tumor with an invasive growth pattern. The expression of adherens junction and desmosomal components were compared with that of cult ured normal oral keratinocytes. Lack of membrane association in interdesmos omal areas, the disorganization of the actin cytoskeleton and the faster ce ll disassembly upon E-cadherin antibody binding in SCCA cells indicated dec reased functional adherens junctions. These observations were supported by a significant reduction in E-, N-, and P-cadherin protein expression. In co ntrast, the level of desmosomal cadherin proteins, desmoglein 1/2 and desmo collin 2, were substantially upregulated and accompanied, ultrastructurally , by increased number and size of desmosomes. Since tumor invasion suppress or capacity has been proposed for desmosomal cadherins, we investigated the in vivo invasion potential of these SCCA cells by introducing them into SC ID mice. Tumors developed, but with a benign phenotype. Based on these resu lts, we hypothesize that the benign behavior of this SCCA cell line is a co nsequence of overexpressed desmosomal cadherins. This SCCA cell line, there fore, represents an excellent model system to further investigate the regul ation and tumor invasion suppressor potential of desmosomal adhesion molecu les.