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Expression and Function of Macrophage Migration Inhibitory Factor in the Pathogenesis of UV‐Induced Cutaneous Nonmelanoma Skin Cancer †
Author(s) -
Heise Ruth,
VetterKauczok Claudia S.,
Skazik Claudia,
Czaja Katharina,
Marquardt Yvonne,
Lue Hongqi,
Merk Hans F.,
Bernhagen Jürgen,
Baron Jens M.
Publication year - 2012
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2012.01108.x
Subject(s) - macrophage migration inhibitory factor , pathogenesis , skin cancer , cancer research , carcinogenesis , actinic keratosis , cytokine , epidermodysplasia verruciformis , hacat , immunology , biology , cancer , medicine , pathology , cell culture , virus , genetics , basal cell
Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB‐induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme‐linked immunosorbent assay studies showed a time‐dependent increase in MIF secretion after a moderate single‐dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNγ upregulated CD74 surface expression in these cells. Affymetrix ® Gene Chip analysis revealed that only keratinocytes prestimulated with IFNγ are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment.