ENDOGENEOUSLY REGULATED SITE-SPECIFIC DIFFERENTIATION OF HUMAN PALMARSKIN KERATINOCYTES IN ORGANOTYPIC COCULTURES AND IN NUDE-MOUSE TRANSPLANTS

Palmar and plantar epidermis is characterized by specific features suc h as the development of a striking lucidum, a very thick stratum corne um, prominent rete ridges and the unique expression of keratin K9. Usi ng organotypic cocultures of keratinocytes and fibroblasts, we investi gated to which extent the specific phenotype of palmar keratinocytes i s maintained in vitro and under systemic host influences after transpl antation onto nude mice. In vitro, palmar keratinocytes developed a th ick epithelium with a prominent, although parakeratotic stratum corneu m showing no significant differences in proliferation and differentiat ion in coculture with either palmar or nonpalmoplantar fibroblasts. Al l differentiation markers including kerato-hyaline and membrane coatin g granules as well as keratin K9 were also found, but at reduced level s and with slightly altered localization, In transplants, substantial normalization towards the palmar phenotype occurred. In 3-week-old gra fts, a homeostatic state was reached, as illustrated by a constant thi ckness of the stratum Malpighii, presence of keratin K10 throughout th e entire suprabasal compartment, increased numbers of K9- and filaggri n-positive cells, and reduction of keratins K16 and K17. At the ultras tructural level, numerous membrane coating granules and an enlargement of keratohyaline granules were seen accordingly, and immunofluorescen ce showed intense continuous lining of the dermo-epidermal junction by laminin, type IV collagen and integrin alpha(6). The high percentage of bromodesoxyuridine-positive cells, mainly in the basal compartment, underlined the hyproproliferative state, comparable to palmoplantar e pidermis.In conclusion, (i) palmar keratinocytes can preserve the pote ntial to express their specific phenotype upon transfer to culture con ditions, and (ii) this intrinsic property is not significantly modulat ed by the type of cocultured fibroblasts. This suggests that fibroblas ts act primarily by sustaining keratinocyte proliferation which is per missive for the fully differentiated phenotype.