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口腔鳞状细胞癌中的基质金属蛋白酶系统

The matrix metalloproteinase system in oral squamous cell carcinoma.

作者信息

Baker E A, Leaper D J, Hayter J P, Dickenson A J

机构信息

Professorial Unit of Surgery, University Hospital of North Tees, Stockton on Tees TS19 8PE, UK.

出版信息

Br J Oral Maxillofac Surg. 2006 Dec;44(6):482-6. doi: 10.1016/j.bjoms.2005.10.005. Epub 2005 Dec 9.

Abstract

BACKGROUND

The matrix metalloproteinase (MMP) system is responsible for degradation of tissue in both normal and pathological processes, including tumour invasion and metastasis.

AIM

To compare tissue concentrations of components of the MMP system between tumour tissue and normal tissue in patients with oral squamous cell carcinoma, and to correlate concentrations with pathological grade of tumour.

METHODS

Thirty-eight paired tissue samples from tumours and normal tissue were analysed by three laboratory techniques: firstly, enzyme linked immunosorbent assays (ELISA) in ng/mg protein for MMP-1, MMP-3, and tissue inhibitors of metalloproteinases (TIMPs) -1 and -2. Secondly, gelatinase activity assays to measure concentrations of total and endogenous active gelatinases, MMP-2 and MMP-9 (ng/mg protein). And thirdly to use quenched fluorescent substrate hydrolysis to measure total MMP activity (pM/min).

RESULTS

The concentration of all MMPs was significantly higher in tumour than in normal oral tissue (p < 0.05, Mann-Whitney U-test). Tissue concentrations of some of these factors correlated with clinical and pathological indices of aggressiveness of tumours, including T-stage, N-stage, tumour differentiation, and anatomical level of involved nodes. However, the study was not powered to show statistical significance.

CONCLUSION

It is the balance between proteinases and their inhibitors that controls tissue degradation at each stage of tumour invasion and metastasis. Measurement of MMPs in oral mucosal biopsy samples may establish the invasive potential of tumours at their initial presentation.

摘要

背景

基质金属蛋白酶(MMP)系统在正常和病理过程中均参与组织降解,包括肿瘤侵袭和转移。

目的

比较口腔鳞状细胞癌患者肿瘤组织与正常组织中MMP系统各成分的组织浓度,并将浓度与肿瘤病理分级相关联。

方法

采用三种实验室技术对38对肿瘤组织和正常组织样本进行分析:首先,用酶联免疫吸附测定法(ELISA)以纳克/毫克蛋白为单位检测MMP-1、MMP-3以及金属蛋白酶组织抑制剂(TIMP)-1和-2。其次,采用明胶酶活性测定法测量总明胶酶和内源性活性明胶酶MMP-2和MMP-9的浓度(纳克/毫克蛋白)。第三,使用淬灭荧光底物水解法测量总MMP活性(皮摩尔/分钟)。

结果

所有MMPs在肿瘤组织中的浓度均显著高于正常口腔组织(p < 0.05,曼-惠特尼U检验)。其中一些因子的组织浓度与肿瘤侵袭性的临床和病理指标相关,包括T分期、N分期、肿瘤分化以及受累淋巴结的解剖水平。然而,该研究的样本量不足以显示统计学意义。

结论

蛋白酶及其抑制剂之间的平衡在肿瘤侵袭和转移的每个阶段控制着组织降解。在口腔黏膜活检样本中检测MMPs可能有助于在肿瘤初发时确定其侵袭潜力。

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