The distribution of the desmosomal protein, plakophilin 1, in human skin and skin tumors

Abstract

Desmosomes are predominant among the types of plaque-bearing adhering junctions found in human skin. These structures contain a set of desmosomal cadherins and cytoplasmic plaque proteins, the synthesis of which is differentiation dependent. As plakophilin 1, a member of the armadillo gene family, is an important accessory desmosomal plaque protein, we raised several monoclonal antibodies specific for this protein and applied immunohistochemical and immunoblotting procedures to study the distribution of plakophilin 1 in desmosomes in adult and fetal skin, psoriatic epidermis, various epithelial skin tumors, and keratinocyte sheets grown in culture. In epidermis, the spinous layers were prominently immunostained by plakophilin 1 antibodies, whereas the basal cell layer was only weakly stained and the stratum corneum was entirely unstained. The staining observed in psoriatic epidermis was somewhat heterogeneous. In hair follicles, the outer root sheath (ORS) was delineated in its suprabasal cell layers, with variable staining in its upper and lower parts. All basal cells of the ORS remained unstained, as did upper inner root sheath (IRS) and matrix cells of lower bulb. In eccrine sweat glands, the reaction was confined to inner dermal ductal cells, with the acini remaining unstained. The desmosomal immunostaining observed in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) was very heterogeneous: In general, junctions in well-differentiated stratified tumor regions were more intensely stained than sections of poorly differentiated and invasively growing BCCs and SCCs. Plakophilin 1 was also prominent in the desmosomes of keratinocyte sheets grown in culture. The cell type-specific, i.e., differentiation-dependent, distribution of desmosomal plakophilin 1 is discussed in relation both to the stratification of the cutaneous epithelia and to tumor differentiation and growth.