Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis
Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis
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DOI：
10.1111/j.0022-202x.2005.23640.x
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发表时间：
2005-04-01
影响因子：
6.5
通讯作者：
Saarialho-Kere, U
中科院分区：
文献类型：
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作者：
Ahokas, K;Skoog, T;Saarialho-Kere, U
基质溶素-2（matrix metalloproteinase，MMP-26）是MMP家族的一种小分子蛋白，在一些上皮癌和正常组织中表达。我们研究了它在良性皮肤疾病中的作用，其特征在于上皮细胞增殖、伤口修复、皮肤癌和角质形成细胞（KC）培养物中的调节。MMP-26在创伤修复过程中的迁移区域中由层粘连蛋白-5阳性KC表达，在以炎症和基底膜微破裂为特征的良性皮肤疾病中，但在完整皮肤中仅在毛囊中表达。在癌前病变的非典型KC中偶尔检测到，但在基底细胞癌岛中未检测到。虽然MMP-26在I级和II级鳞状细胞癌（SCC）中表达，但在去分化的III级肿瘤中不存在。MMP-26既不与其同源物matrilysin-1共表达，也不与增殖标志物Ki-67共表达。但在组织样本中，它与肿瘤抑制因子p16共定位或在相同区域的相邻细胞中检测到。在KC和HaCaT细胞培养物中，12-佛波醇-13-肉豆蔻酸酯-乙酸酯、表皮生长因子、肿瘤坏死因子-α、转化生长因子-β 1、白细胞介素-1（IL-1）β、IL-6、胰岛素样生长因子、γ-IFN、视黄酸、地塞米松、四种基质或ras-转化不能上调MMP-26表达。MMP-26的表达模式表明，即使没有肿瘤发生，由于细胞-基质相互作用和炎症的改变，它也可能在基底KC中上调，并且与大多数MMP不同，在SCC的组织学去分化期间下调。因此，SCC中MMP-26的缺乏可能是侵袭性生长的标志。
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.