title: The 'Abtropfung phenomenon' revisited: Dermal nevus cells from congenital nevi cannot activate matrix metalloproteinase 2 (MMP-2).
abstract: Since Unna's Abtropfung hypothesis, the process of migration of nevus cells in the dermis remains unknown. To investigate its mechanisms, we studied the role of gelatinases in dermal nevus cells obtained from congenital pigmented nevi, which are major actors in the remodeling of basement membrane proteins. Our previous studies have shown that dermal nevus cells express pro-matrix metalloproteinase (MMP)-2 exclusively and cannot return to the dermis when seeded together with keratinocytes on top of the dermis in a skin reconstruction model. To examine why MMP-2 was not in its active form, we used Western blot to study the expression of members of the MMP-2 activation pathway (membrane type 1-MMP and tissue inhibitor of metalloproteinase-2), which proved to be normally expressed. To induce the dermal passage of nevus cells artificially, we also tried to activate gelatinases with phorbol-12-myristate-13-acetate and epidermal growth factor, using epidermis reconstructed with nevus cells. No migration in the dermis could be triggered. We conclude that the absence of active MMP-2 is due to a functional blockade of its activation pathway and may prevent dermal nevus cells from reaching the dermal compartment in skin reconstructs. Furthermore, our findings reinforce the concept that dermal nevus cells originating from congenital nevi are in a quiescent status.
authors.affiliation: Inserm EMI-U 02-17, Unité de Dermatologie, Université Victor Ségalen, Bat TP ouest 4ème Etage, Bordeaux Cedex, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Gontier
authors.forename: Muriel
authors.initials: M
authors.lastname: Cario-André
authors.forename: Pierre
authors.initials: P
authors.lastname: Vergnes
authors.forename: Jozef
authors.initials: J
authors.lastname: Bizik
authors.forename: Jean-Etienne
authors.initials: JE
authors.lastname: Surlève-Bazeille
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
mesh_terms: D000293:Adolescent; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008545:Melanoma / Q000737:chemistry; D009506:Nevus / Q000151:congenital*; D009508:Nevus, Pigmented / Q000737:chemistry; D012878:Skin Neoplasms / Q000151:congenital*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D019716:Tissue Inhibitor of Metalloproteinase-2; D004815:Epidermal Growth Factor; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D013755:Tetradecanoylphorbol Acetate