Cathepsin B promotes both motility and invasiveness of oral carcinoma cells.
Cathepsin B promotes both motility and invasiveness of oral carcinoma cells.
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DOI：
10.1016/j.abb.2005.01.023
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发表时间：
2005-04
影响因子：
3.9
通讯作者：
N. Wickramasinghe;N. Nagaraj;N. Vigneswaran;W. Zacharias
中科院分区：
文献类型：
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作者：
N. Wickramasinghe;N. Nagaraj;N. Vigneswaran;W. Zacharias
我们先前的研究表明，组织蛋白酶B（CB）蛋白酶在口腔鳞状细胞癌中的过度表达与肿瘤的晚期和组织学恶性程度低呈正相关。在这里，我们研究CB是否有助于口腔癌细胞的侵袭性。针对RNA介导的抑制作用，设计了两种靶向CB mRNA的核酶，并在口腔鳞状细胞癌细胞系1386 Tu中稳定表达。通过定量实时PCR、蛋白质印迹和蛋白酶活性测定，两种核酶均降低CB mRNA、蛋白质和活性的表达，而不影响组织蛋白酶D或β-肌动蛋白。基质胶侵袭测定表明，细胞的侵袭性显着降低所表达的核酶，令人惊讶的是，核酶转染的细胞的运动性也减少。我们的研究结果证明CB在促进口腔癌扩散和侵袭中的直接作用，并为通过RNA抑制剂策略靶向CB控制口腔癌恶性和转移提供了可能性。
We previously demonstrated that overexpression of cathepsin B (CB) protease in oral squamous cell carcinomas correlated positively with advanced tumor stage and poor histologic malignancy grade. Here we examined whether CB contributes to the invasiveness of oral carcinoma cells. For RNA-mediated inhibition, two ribozymes that target CB mRNA were designed and stably expressed in the oral squamous cell carcinoma cell line 1386Tu. Both ribozymes diminished expression of CB mRNA, protein, and activity, without affecting cathepsin D or β-actin, as determined by quantitative real-time PCR, Western blots, and protease activity assays. Matrigel invasion assays showed that the invasiveness of the cells was significantly reduced by the expressed ribozymes and, surprisingly, the motilities of the ribozyme-transfected cells were also diminished. Our results document a direct role for CB in promoting oral cancer spread and invasion, and open the possibility of controlling oral carcinoma malignancy and metastasis by targeting CB with RNA inhibitor strategies.