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金属蛋白酶及其抑制剂:对头颈部鳞状细胞癌肿瘤侵袭性和转移形成的影响

Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas.

作者信息

Görögh Tibor, Beier Ulf H, Bäumken Jens, Meyer Jens E, Hoffmann Markus, Gottschlich Stefan, Maune Steffen

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University of Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 14, 24105 Kiel, Germany.

出版信息

Head Neck. 2006 Jan;28(1):31-9. doi: 10.1002/hed.20298.

DOI:10.1002/hed.20298
PMID:16265652
Abstract

BACKGROUND

Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC).

METHODS

Of 48 laryngeal squamous cell carcinoma (LSCC) biopsies and 10 HNSCC cell lines, mRNA was isolated, reversely transcribed, and subjected to polymerase chain reaction (PCR) amplifying MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, and TIMP-2. Silver nitrate-stained gel electrophoresis demonstrated MMP and TIMP expression status. Exemplary immunohistochemistry and zymography confirmed translation and enzyme activity.

RESULTS

Densitometric analysis revealed MMP-2 expression and lymph node metastases to be positively and TIMP-1 and TIMP-2 to be negatively correlated with lymph node metastases. TIMP-2 expression and tumor size were negatively correlated. MMP-1, MMP-9, and MMP-10 expression were not correlated to metastasis formation or tumor size.

CONCLUSIONS

Our results suggest that MMP-2 expression enhances, whereas TIMP-1 and TIMP-2 both suppress, cancer spread in LSCC.

摘要

背景

基质金属蛋白酶(MMPs)在肿瘤侵袭中起重要作用。本研究调查头颈部鳞状细胞癌(HNSCC)中MMPs和金属蛋白酶组织抑制剂(TIMPs)的表达状况。

方法

对48份喉鳞状细胞癌(LSCC)活检样本和10种HNSCC细胞系,分离mRNA,反转录,并进行聚合酶链反应(PCR)扩增MMP-1、MMP-2、MMP-9、MMP-10、TIMP-1和TIMP-2。硝酸银染色凝胶电泳显示MMP和TIMP的表达状况。典型的免疫组织化学和酶谱分析证实了翻译和酶活性。

结果

光密度分析显示MMP-2表达与淋巴结转移呈正相关,TIMP-1和TIMP-2与淋巴结转移呈负相关。TIMP-2表达与肿瘤大小呈负相关。MMP-1、MMP-9和MMP-10的表达与转移形成或肿瘤大小无关。

结论

我们的结果表明,MMP-2表达增强,而TIMP-1和TIMP-2均抑制LSCC中的癌症扩散。

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