The clinical significance of cathepsin S expression in human astrocytomas
The clinical significance of cathepsin S expression in human astrocytomas
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DOI：
10.1016/s0002-9440(10)63641-3
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发表时间：
2003-07-01
影响因子：
6
通讯作者：
Johnston, PG
中科院分区：
文献类型：
--
作者：
Flannery, T;Gibson, D;Johnston, PG
星形细胞瘤早期局部侵袭。即使在明显的完全手术切除后，细胞也会导致肿瘤复发，导致与恶性星形细胞瘤相关的不良预后。蛋白水解酶与促进肿瘤细胞侵袭有关，当前的研究旨在表征星形细胞瘤中半胱氨酸蛋白酶组织蛋白酶 S (CatS) 的表达，并检查其在侵袭中的潜在作用。活检的免疫组织化学分析表明，CatS 在星形细胞瘤细胞中表达，但在正常星形胶质细胞、少突胶质细胞、神经元和内皮细胞中不表达。小胶质细胞和巨噬细胞也呈阳性。 59 个星形细胞瘤活组织检查中的比活性测定证实了 CatS 表达，此外还证明了 IV 级肿瘤中表达的活性水平最高。 CatS 活性也存在于体外星形细胞瘤细胞中，并且细胞外活性水平在源自 IV 级肿瘤的培养物中最高。使用 U251MG 细胞系进行体外侵袭测定，在选择性 CatS 抑制剂 4-吗啉脲-LeuHomoPhe-乙烯基砜存在下，侵袭率降低高达 61%。我们得出结论，星形细胞瘤中 CatS 表达上调。细胞并为 CatS 在侵袭中的潜在作用提供证据。
Early local invasion by astrocytoma. cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine proteinase cathepsin S (CatS) in astrocytomas and examine its potential role in invasion. Immunohistochemical analysis of biopsies demonstrated that CatS was expressed in astrocytoma cells but absent from normal astrocytes, oligodendrocytes, neurones and endothelial cells. Microglial cells and macrophages were also positive. Assays of specific activity in 59 astrocytoma biopsies confirmed CatS expression and in addition demonstrated that the highest levels of activity were expressed in grade IV tumors. CatS activity was also present in astrocytoma cells in vitro and the extracellular levels of activity were highest in cultures derived from grade IV tumors. In vitro invasion assays were carried out using the U251MG cell line and the invasion rate was reduced by up to 61% in the presence of the selective CatS inhibitor 4-Morpholineurea-LeuHomoPhe-vinylsulphone. We conclude that CatS expression is up-regulated in astrocytoma. cells and provide evidence for a potential role for CatS in invasion.