Cathepsin B and glioma invasion
Cathepsin B and glioma invasion
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DOI：
10.1016/s0736-5748(99)00011-8
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发表时间：
1999-08-01
影响因子：
1.8
通讯作者：
Sloane, BF
中科院分区：
文献类型：
--
作者：
Demchik, LL;Sameni, M;Sloane, BF
组织蛋白酶B的表达增加已在许多人类和动物肿瘤中报道。这也已经在人神经胶质瘤中观察到，其中组织蛋白酶B mRNA、蛋白质、活性和分泌的增加与恶性进展平行。在本研究中，我们发现组织蛋白酶B直接参与胶质瘤细胞的侵袭。组织蛋白酶B活性在胶质瘤组织中比在匹配的正常脑组织中高一个数量级。半胱氨酸蛋白酶抑制剂在两种体外模型中减少了胶质瘤细胞的侵袭：通过基质胶的侵袭和胶质瘤球体向正常脑聚集体的浸润。胶质瘤球状体比单层表达更高水平的组织蛋白酶B，并且组织蛋白酶B活性不同的亚克隆浸润正常脑聚集体的能力与其组织蛋白酶B活性不同。我们证实，细胞内染色的组织蛋白酶B发生在细胞周边和细胞过程中，并观察到细胞表面上的细胞外染色。此外，我们还证实了位于细胞周边和突起内的细胞内组织蛋白酶B是有活性的。细胞表面组织蛋白酶B与细胞外基质组分的降解区域共定位。我们推测，胶质瘤中活性组织蛋白酶B表达的增加导致了体外和体内侵袭的增加，并建立了一种异种移植模型，在该模型中可以验证这一假设。(C)1999年ISDN。出版社：Elsevier Science Ltd版权所有。
Increased expression of cathepsin B has been reported in a number of human and animal tumors. This has also been observed in human gliomas where increases in cathepsin B mRNA, protein, activity and secretion parallel malignant progression. In the present study, we showed that cathepsin B was directly involved in glioma cell invasion. Activity of cathepsin B was an order of magnitude higher in glioma tissue than in matched normal brain. Inhibitors of cysteine proteases reduced invasion of glioma cells in two in vitro models: invasion through Matrigel and infiltration of a glioma spheroid into a normal brain aggregate. Glioma spheroids expressed higher levels of cathepsin B than did monolayers and the ability of subclones differing in cathepsin B activity to infiltrate normal brain aggregates paralleled their cathepsin B activity. We confirmed that intracellular staining for cathepsin B occurs at the cell periphery and in cell processes and observed extracellular staining on the cell surface. In addition, we demonstrated that intracellular cathepsin B located at the cell periphery and in processes was active. The cell surface cathepsin B colocalized with areas of degradation of an extracellular matrix component. We hypothesize that the increased expression of active cathepsin B in gliomas leads to increases in invasion bz vitro and in vivo and have developed a xenotransplant model in which this hypothesis can be tested. (C) 1999 ISDN. Published by Elsevier Science Ltd All rights reserved.