Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis

被引:49
作者
Ahokas, K
Skoog, T
Suomela, S
Jeskanen, L
Impola, U
Isaka, K
Saarialho-Kere, U [1 ]
机构
[1] Soder Sjukhuset, Karolinska Inst, Dept Dermatol, Plan 5, S-11883 Stockholm, Sweden
[2] Univ Helsinki, Cent Hosp, Biomedicum Helsinki, Dept Dermatol, Helsinki, Finland
[3] Karolinska Inst, Novum, Clin Res Ctr, Huddinge, Sweden
[4] Karolinska Inst, Novum, Dept Biosci, Huddinge, Sweden
[5] Tokyo Med Univ, Dept Obstet & Gynecol, Tokyo, Japan
基金
芬兰科学院;
关键词
beta-catenin; E-cadherin; laminin-5; MMP-7; MMP-9; p16;
D O I
10.1111/j.0022-202X.2005.23640.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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-alpha, transforming growth factor-beta 1, interleukin-1 (IL-1)beta, IL-6, insulin-like growth factor, gamma-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.
引用
收藏
页码:849 / 856
页数:8
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