Cathepsin B: multiple roles in cancer.
Cathepsin B: multiple roles in cancer.
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DOI：
10.1002/prca.201300105
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Sloane BF
中科院分区：
文献类型：
--
作者：
Aggarwal N;Sloane BF
蛋白酶，包括细胞内蛋白酶，在恶性进展的许多不同阶段发挥作用。我们的重点是组织蛋白酶B，一种溶酶体半胱氨酸组织蛋白酶。在多种人类癌症中发现高水平的组织蛋白酶B，其水平通常诱导组织蛋白酶B分泌并与肿瘤细胞膜结合。在实验模型中，如鼠胰腺癌和乳腺癌的转基因模型，组织蛋白酶B的因果作用已被证明在起始、生长/肿瘤细胞增殖、血管生成、侵袭和转移中。转基因模型中的肿瘤生长由肿瘤相关细胞（例如肿瘤相关巨噬细胞）以及肿瘤细胞中的组织蛋白酶B促进。在转基因模型中，组织蛋白酶B的缺乏与增强的细胞凋亡有关，然而组织蛋白酶B也被证明有助于细胞凋亡。组织蛋白酶B是在人神经胶质瘤异种移植模型中鉴定的蛋白水解途径的一部分;在这些肿瘤中仅靶向组织蛋白酶B比靶向组织蛋白酶B与其他蛋白酶或蛋白酶受体的组合更不有效。需要了解肿瘤中组织蛋白酶B表达增加的机制以及组织蛋白酶B与肿瘤细胞膜的相关性，以确定靶向组织蛋白酶B是否具有治疗益处。
Proteases, including intracellular proteases, play roles at many different stages of malignant progression. Our focus here is cathepsin B, a lysosomal cysteine cathepsin. High levels of cathepsin B are found in a wide variety of human cancers, levels that often induce secretion and association of cathepsin B with the tumor cell membrane. In experimental models, such as transgenic models of murine pancreatic and mammary carcinomas, causal roles for cathepsin B have been demonstrated in initiation, growth/tumor cell proliferation, angiogenesis, invasion, and metastasis. Tumor growth in transgenic models is promoted by cathepsin B in tumor-associated cells, for example, tumor-associated macrophages, as well as in tumor cells. In transgenic models, the absence of cathepsin B has been associated with enhanced apoptosis, yet cathepsin B also has been shown to contribute to apoptosis. Cathepsin B is part of a proteolytic pathway identified in xenograft models of human glioma; targeting only cathepsin B in these tumors is less effective than targeting cathepsin B in combination with other proteases or protease receptors. Understanding the mechanisms responsible for increased expression of cathepsin B in tumors and association of cathepsin B with tumor cell membranes is needed to determine whether targeting cathepsin B could be of therapeutic benefit.
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