Journal
EXPERIMENTAL DERMATOLOGY
Volume 18, Issue 12, Pages 1044-1052Publisher
WILEY
DOI: 10.1111/j.1600-0625.2009.00901.x
Keywords
cyclosporin; immunosuppression; mice; NF-kappa B; skin cancer
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Funding
- Academy of Finland [115590, 108828]
- Sigrid Juselius Foundation
- Finska Lakaresallskapet
- Helsinki University Central Hospital Research Fund, Finland [TYH6241]
- Cancerfonden (US-K)
- Swedish Research Council (US-K)
- Welander-Finsen Foundation (TS), Sweden
- Academy of Finland (AKA) [115590, 115590, 108828, 108828] Funding Source: Academy of Finland (AKA)
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The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases ( MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed ( IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-kappa B signalling were performed. Semiquantitatively assessed stromal MMP-10 expression was higher (P = 0.009) in the control group when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression did not differ between the groups but stromal fibroblasts of the control SCCs tended to express MMP-21 more abundantly. MMP-10 expression was observed already in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and invasive cancer were negative. Our results suggest that MMP-10 may be important in the initial stages of SCC progression and induced in the stroma relating to the general host-response reaction to skin cancer. MMP-21 does not associate with invasion of SCC but may be involved in keratinocyte differentiation.
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