The main objective of this proposal is to compare two epidermal cell adhesion complexes, a dystroglycan-containing complex (DGC) and the hemidesmosomes. Hemidesmosomes and the DGC are transmembrane receptor complexes that serve to connect the extracellular matrix and the cytoskeleton and are essential to maintain integrity of epidermis and muscle, respectively Severe blistering results from genetic defects in hemidesmosome components while muscular dystrophy develops from defects in DGC components In our preliminary studies, two components of DGC (utrophin & Beta-dystroglycan) were identified in epidermal tissue and uncultured primary keratinocytes Upon culturing, neither components of DGC nor mature hemidesmosomes were detectable This proposal will delineate the composition of the epidermal DGC and its physical and functional relationship with hemidesmosomes in epidermis and in an in vitro system to be developed. Ultrastructural association of DGC and hemidesmosomes will be examined using immunoelectron microscopy while functional interrelatedness will be examined by staining for DGC in tissues that do not form hemidesmosomes Loss of hemidesmosomes or decrease in dystroglycan expression directly correlates with poor prognosis in epithelial cell based cancers The long term goal of this research is to identify the role of the complex(es) in cancer as to better understand the progression and targets of these cancers.
