MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-light.
BACKGROUND
In malignant melanoma, recent studies have demonstrated an important role of matrix-metalloproteinase 2 (MMP-2), its co-activating enzyme membrane-type matrix-metalloproteinase 1 (MT1-MMP), and the endogenous inhibitor of MMP-2, tissue-inhibitor of matrix metalloproteinase 2 (TIMP-2). Melanocytic nevi are benign neoplasms of the melanocytic lineage, but may exhibit dysplastic features that can be difficult to distinguish from early stage melanoma. As shown in earlier studies, nevi show important morphological and phenotypical changes in response to ultraviolet light (UVB) irradiation.


OBJECTIVE
To clarify the role of MMP-2, TIMP-2 and MT1-MMP in UVB-irradiated vs. non-irradiated melanocytic nevi.


METHODS
Immunohistochemical comparison of the MMP-2, TIMP-2 and MT1-MMP expression pattern.


RESULTS
MMP-2 is expressed by lesional keratinocytes and its expression is up-regulated by UVB-irradiation. MMP-2 expression was not observed in melanocytic cells. TIMP-2, by contrast, is predominantly expressed by melanocytic nevus cells, and its expression is in part down-regulated by UVB-irradiation. MT1-MMP is expressed by basal keratinocytes and to a weaker extent by melanocytic nevus cells.


CONCLUSIONS
MMP-2 expression by keratinocytes in nevi probably represents the result of activation of keratinocyte turnover in lesional epidermis. MMP-2 could play a role in the downward movement of junctional nevus cells into the dermis. The reduction of TIMP-2 expression in melanocytic cells by UV-light together with the enhanced expression of MMP-2 in the adjacent epidermis may promote basement membrane degradation. The expression pattern of MT1-MMP in close proximity to epithelial-mesenchymal interfaces underlines the synergistic role of MT1-MMP in this process.
Department of Dermatology, Medical University Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. svenkrengel@gmx.net
Sven
S
Krengel
M
M
Alexander
J
J
Brinckmann
M
M
Tronnier
D000328:Adult; D000368:Aged; D015536:Down-Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014466:Ultraviolet Rays
D019716:Tissue Inhibitor of Metalloproteinase-2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2