Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers.

Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers.
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DOI:
10.1054/bjoc.2000.1634
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发表时间:
2001-03-02
影响因子:
8.8
通讯作者:
Saarialho-Kere, U
Saarialho-Kere, U
中科院分区:
医学1区
文献类型:
--
作者:
Kerkela, E;Ala-aho, R;Lohi, J;Grenman, R;M-Kahari, V;Saarialho-Kere, U

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基质金属蛋白酶家族的几个成员的共同表达是人类恶性肿瘤的特征。为了探讨基质分解素-2(MMP-10)在皮肤肿瘤生长和侵袭中的作用,我们用原位杂交技术研究了高转移能力的皮肤癌(鳞状细胞癌,SCCs)、仅有局部破坏性的肿瘤(基底细胞癌,BCC)和癌前病变(Bowen病和光化性角化病)。比较基质分解素-1(MMP1-3)和基质分解素-1(MMP1-MMP3)的表达与肿瘤侵袭性的关系。13/21例SSCs和11/19例BCC仅在上皮层粘连蛋白5阳性癌细胞中表达,而癌前病变均为阴性。MT1-MMPmRNA在19/21例鳞状细胞癌和14/18例基底细胞癌中仅在成纤维细胞中表达。转化生长因子-α、角质形成细胞生长因子、干扰素-γ联合转化生长因子-β1、肿瘤坏死因子-α可上调皮肤鳞状细胞癌细胞系(UT-SCC-7)MMP10水平。我们的结果表明,根据组织学和MT1-MMPs的表达评估,MMP10的表达与肿瘤的侵袭行为无关,但可能是由与皮肤肿瘤相关的伤口愈合和炎性基质重塑事件诱导的。©2001癌症研究活动http://www.bjcancer.com
Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen's disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-α and keratinocyte growth factor, and by interferon-γ in combination with transforming growth factor-β1 and tumour necrosis factor-α both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com