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O-1N中基质金属蛋白酶-2(MMP-2)表达增加及激活:具有高潜在淋巴结转移的仓鼠口腔鳞状细胞癌

Increased expression and activation of matrix metalloproteinase-2 (MMP-2) in O-1N: hamster oral squamous cell carcinoma with high potential lymph node metastasis.

作者信息

Zhang Y, Wang C, Mizukami H, Itoh H, Kusama M, Ozawa K, Jinbu Y

机构信息

Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical School, Japan.

出版信息

J Exp Clin Cancer Res. 2006 Sep;25(3):417-23.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers with poor clinical outcome. MMP-2 was implied to contribute to the invasiveness and metastatization of various malignancies because of the degradation of type IV collagen. In this experiment, ELISA, Western blot and Q-RT-PCR was performed to investigate the expression and activation of MMP-2 in serum and tumor from hamster oral cancer model with high lymph node metastasis based on the various stages of OSCC development. Active MMP-2 in the serum was found elevated during oral cancer progression. In the metastatic stage, total MMP-2 level was 46% higher than it in the expansive stage, while active MMP-2 level increased 6-fold than it in the expansive stage. MMP-2 serum activation ratio was significantly enhanced in the metastatic stage than before tumor transplantation and that in the expansive stage. MMP-2 protein and MMP-2 mRNA was found to be increased during oral cancer development in hamster models. The increase of MMP-2 expression and activation starts prior to the metastasis occurrence, indicating the important role of MMP-2 in the early phase of oral cancer progression. Active MMP-2 level in serum may be a useful indicator for monitoring oral cancer progression.

摘要

口腔鳞状细胞癌(OSCC)是最常见的头颈部癌症之一,临床预后较差。由于IV型胶原蛋白的降解,MMP-2被认为与各种恶性肿瘤的侵袭和转移有关。在本实验中,基于OSCC发展的不同阶段,采用ELISA、Western blot和Q-RT-PCR方法,研究高淋巴结转移仓鼠口腔癌模型血清和肿瘤中MMP-2的表达及激活情况。发现在口腔癌进展过程中血清中活性MMP-2升高。在转移阶段,总MMP-2水平比扩张阶段高46%,而活性MMP-2水平比扩张阶段增加了6倍。转移阶段MMP-2血清激活率比肿瘤移植前及扩张阶段显著增强。在仓鼠模型中,口腔癌发展过程中MMP-2蛋白和MMP-2 mRNA均增加。MMP-2表达和激活的增加在转移发生之前就开始了,表明MMP-2在口腔癌进展早期起重要作用。血清中活性MMP-2水平可能是监测口腔癌进展的有用指标。

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