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The ‘Abtropfung Phenomenon’ Revisited: Dermal Nevus Cells from Congenital Nevi Cannot Activate Matrix Metalloproteinase 2 (MMP-2)

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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.
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Keywords: Epidermal reconstructs; MMP-2; MMP-9; Nevus cells

Document Type: Research Article

Affiliations: 1: Inserm EMI-U 02-17, Unité de Dermatologie, Université Victor Ségalen, Bat TP ouest 4ème Etage, Bordeaux Cedex, France; 2: Service de Chirurgie Pédiatrique, Hôpital Pellegrin-Enfants, Place Amélie Raba Léon, Bordeaux, France; 3: Department of Tumor Cell Biology, Cancer Research Institute, Bratislava, Slovakia 4: Laboratoire Facteurs de Défense et de Régulation Cellulaire, Université Bordeaux I, UFR de Sciences biologiques, Bat de Biologie Animale, Av. des Facultés, Talence, France;

Publication date: 01 August 2003

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