title: Undifferentiated keratinocytes control growth, morphology, and antigen expression of normal melanocytes through cell-cell contact.
abstract: BACKGROUND
  Melanocytes in the normal human epidermis are generally dendritic and neither proliferate nor express melanoma-associated antigens. In culture, on the other hand, melanocytes are bi- to tripolar, proliferate with 2 to 4 day doubling times, and express melanoma-associated antigens. This observation prompted us to investigate the regulatory role of keratinocytes for growth, morphology, and antigen expression of melanocytes.
  
  
  METHODS
  Melanocytes and keratinocytes were cultured under three different co-culture conditions: (a) separated by a semiporous membrane, (b) in monolayer cultures allowing direct contact between cells, and (c) in three-dimensional epidermal reconstructs.
  
  
  RESULTS
  Melanocytes separated from keratinocytes by semiporous membranes remained di- and tripolar and could not proliferate in medium optimal for keratinocytes. When cell-cell contact was established between melanocytes and undifferentiated, but not differentiated, keratinocytes, melanocytes proliferated at a rate similar to keratinocytes and they developed multiple dendrites. In co-cultures allowing the multi-layered growth of keratinocytes, melanocytes were nonproliferative when juxtaposed to undifferentiated keratinocytes in the basal layer, but proliferated when surrounded by differentiated keratinocytes in the intermediate and upper layers. Expression of melanoma-associated antigens on melanocytes decreased to similar levels as in normal skin when melanocytes were in direct contact with undifferentiated, but not differentiated, keratinocytes.
  
  
  CONCLUSIONS
  Undifferentiated, but not differentiated, keratinocytes control growth, morphology, and antigen expression of melanocytes through direct cell-cell contact. These results suggest that the phenotypic characteristics of nevus and melanoma cells in the dermis, i.e., proliferation and expression of tumor-associated antigens, may be due to their loss of contact with undifferentiation keratinocytes.
authors.affiliation: Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
authors.forename: I T
authors.initials: IT
authors.lastname: Valyi-Nagy
authors.forename: G
authors.initials: G
authors.lastname: Hirka
authors.forename: P J
authors.initials: PJ
authors.lastname: Jensen
authors.forename: I M
authors.initials: IM
authors.lastname: Shih
authors.forename: I
authors.initials: I
authors.lastname: Juhasz
authors.forename: M
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D000941:Antigens / Q000276:immunology*; D002450:Cell Communication; D002455:Cell Division; D017077:Culture Media, Conditioned; D003584:Cytological Techniques; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008544:Melanocytes / Q000166:cytology* / Q000276:immunology*; D012016:Reference Values
chemical_list: D000941:Antigens; D017077:Culture Media, Conditioned