1. ^*Department of Dermatology, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland;
2. ^†University of Helsinki, Helsinki, Finland;
3. ^‡Clinical Research Center and Department of Biosciences at Novum, Huddinge, Sweden;
4. ^§Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo, Japan;
5. ^¶Department of Dermatology, Karolinska Institutet, Stockholm Söder Hospital, Stockholm, Sweden

Correspondence: Ulpu Saarialho-Kere MD, PhD, and Prof, Department of Dermatology, Plan 5, Södersjukhuset, S-11883 Stockholm, Sweden. Email: ulpu.saarialho-kere@helsinki.fi

Received 24 September 2004; Revised 5 November 2004; Accepted 17 November 2004.

Abstract

Matrilysin-2 (matrix metalloproteinase (MMP)-26) is a small protein of the MMP family expressed in some epithelial carcinomas and normal tissues. We studied its role in benign skin disorders characterized by epithelial proliferation, in wound repair, skin cancer, and regulation in keratinocyte (KC) cultures. MMP-26 is expressed by laminin-5-positive KC in the migrating area during wound repair, in benign skin disorders characterized by inflammation and microdisruptions of basement membrane, but in intact skin only in hair follicles. It was detected in occasional atypical KC in pre-malignant lesions but not in basal cell cancer islands. Although MMP-26 was expressed in grades I and II squamous cell cancers (SCC), it was not present in dedifferentiated grade III tumors. MMP-26 was neither co-expressed with its close homologue matrilysin-1 nor with the proliferation marker Ki-67. But in tissue samples it either co-localized or was detected in adjacent cells of same regions with the tumor suppressor p16. In KC and HaCaT cell cultures, 12-phorbol-13-myristate-acetate, epidermal growth factor, tumor necrosis factor-, transforming growth factor-1, interleukin-1 (IL-1), IL-6, insulin-like growth factor, -IFN, retinoic acid, dexamethasone, four matrices or ras-transformation were unable to upregulate MMP-26 expression. The expression pattern of MMP-26 suggests that it may be upregulated in basal KC even without tumorigenesis because of altered cell–matrix interactions and inflammation and, unlike most MMP, becomes downregulated during histological dedifferentiation of SCC. Thus, lack of MMP-26 in SCC could be a marker of aggressive growth.