Purification and characterization of the endoglycosidase heparanase 1 fromhuman plantar stratum corneum: a key enzyme in epidermal physiology?

A protein exhibiting endoglycosidase activity was purified from plantar str atum corneum to apparent homogeneity in two sequential column chromatograph ic steps. Protein sequencing revealed its identity with the recently cloned human heparanase 1, an enzyme, the expression of which is reported to be r elated to the metastasic potential of tumor cells. By using a heparanase 1 specific antibody we were able to demonstrate that, in the plantar stratum corneum, heparanase 1 exists in two forms, the active 50 kDa protein and th e inactive 63 kDa form, probably a proform of the enzyme. The antibody also decorated numerous degradation fragments. Reverse transcription polymerase chain reaction studies as well as immunohistochemical analysis using recon structed and normal human epidermis demonstrated clearly a keratinocyte dif ferentiation related expression of heparanase 1. Interestingly, the antibod y also strongly decorated dendritic cells, which after double labeling coul d be identified to be a subpopulation of the epidermal Langerhans cells. Ba sed on our findings and the known history of this enzyme, we advanced the h ypothesis that heparanase 1 has multiple physiologic functions in the epide rmis: (i) it plays an important role in epidermal differentiation, possibly by modulating the liberation of heparan sulfate bound (growth) factors; (i i) in the stratum corneum, the endoglycosidase activity of heparanase 1 mig ht be indispensable and represent the first step in the desquamation proces s; and (iii) in Langerhans cells, its catalytic activity is required for th e trans-tissue migration of these cells.