Invasiveness of transformed human breast epithelial cell lines is related to cathepsin B and inhibited by cysteine proteinase inhibitors
Invasiveness of transformed human breast epithelial cell lines is related to cathepsin B and inhibited by cysteine proteinase inhibitors
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DOI：
10.1515/bc.2003.050
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发表时间：
2003-03-01
影响因子：
3.7
通讯作者：
Lah, TT
中科院分区：
文献类型：
--
作者：
Bervar, A;Zajc, I;Lah, TT
溶酶体半胱氨酸蛋白酶组织蛋白酶B和L的活性受其内源性抑制剂stefins A和B以及半胱氨酸蛋白酶抑制剂C的调节，它们的失衡可能与恶性细胞表型的侵袭性增加和发展有关。本研究的目的是调查上述蛋白质的mRNA，蛋白质和活性水平的关系，在体外侵袭性和报告的体内致瘤性的四个人乳腺癌细胞系：自发永生化细胞系MCF10A，其cHaras转染MCF10AT，和两个致瘤衍生细胞系，MCF10ATCa1a和MCF10ATCa1d。侵袭性与致瘤性无关，因为MCF 10AT细胞是最具侵袭性的，其余三种细胞的侵袭性约为其水平的一半。组织蛋白酶B的表达在所有表达水平上都能抑制体外基质胶的侵袭性，但组织蛋白酶L不能。在致瘤细胞系中，Stefin水平升高数倍，但在MCF10AT中未升高。组织蛋白酶B在乳腺癌细胞系的侵袭中起积极作用的假设被合成的半胱氨酸蛋白酶抑制剂，特别是对组织蛋白酶B具有选择性的抑制剂，显著降低MCF 10 AT细胞的侵袭的事实所证实。
The activities of the lysosomal cysteine proteinases cathepsin B and L are regulated by their endogenous inhibitors, stefins A and B, and cystatin C, and their imbalance may be associated with increased invasiveness and development of the malignant cell phenotype. The aim of this study was to investigate mRNA, protein and activity levels of the above proteins in relation to in vitro invasiveness and to the reported in vivo tumorigenicity of four human breast tumor cell lines: the spontaneously immortalized cell line MCF10A, its cHaras transfectant MCF10AT, and two tumorigenic derivative cell lines, MCF10ATCa1a and MCF10ATCa1d. Invasiveness did not correlate with tumorigenicity, since the MCF10AT cell was the most invasive and the remaining three were at about half of its level. Cathepsin B expression paralleled the in vitro invasiveness through matrigel at all levels of expression, but cathepsin L did not. Stefin levels were elevated severalfold in the tumorigenic cell lines, but not in MCF10AT. The hypothesis that cathepsin B plays an active role in the invasion of breast cancer cell lines was confirmed by the fact that synthetic cysteine proteinase inhibitors, particularly those selective for cathepsin B, significantly reduced the invasion of the MCF10AT cells.