Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma - A possible in vitro model of the histogenesis of dermatofibroma

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD14(+) peripheral blood monocytes to which IL-4 and GM-CSF were added. Using these monocyte-derived DCs, we examined the ability of various cytokines, such as IL-1 beta, IL-3, IL-5, IL-6, IL-7, IL-8, ILIO, TNF alpha, TGF beta, M-CSF, IFN alpha, and IFN gamma, and phorbol 12-myristate 13-acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a magnitude similar to that of non-treated monocyte-derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells. These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.