DEGRADATION OF EXTRACELLULAR-MATRIX PROTEINS BY HUMAN CATHEPSIN-B FROM NORMAL AND TUMOR-TISSUES
DEGRADATION OF EXTRACELLULAR-MATRIX PROTEINS BY HUMAN CATHEPSIN-B FROM NORMAL AND TUMOR-TISSUES
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DOI：
10.1042/bj2820273
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发表时间：
1992-02-15
影响因子：
4.1
通讯作者：
SLOANE, BF
中科院分区：
文献类型：
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作者：
BUCK, MR;KARUSTIS, DG;SLOANE, BF
我们的实验室先前已经证明，几种组织学类型的人类和动物肿瘤的恶性程度增加与其组织蛋白酶B活性的增加有关，特别是与质膜/内体囊泡或脱落囊泡有关的组织蛋白酶B活性。 在这里，我们报告，组织蛋白酶B从正常或肿瘤组织降解纯化的细胞外基质成分，IV型胶原蛋白，层粘连蛋白和纤连蛋白，在酸性pH值和中性pH值。降解产物的数量和大小进行了分析，SDS/PAGE。 来自两种来源的组织蛋白酶B对细胞外基质蛋白表现出相似的活性和相似的切割模式。 在中性pH值下，来自两种来源的组织蛋白酶B似乎经历自降解，这是一个在替代底物如细胞外基质蛋白存在下降低的过程。 组织蛋白酶B在25 ℃下容易降解IV型胶原，表明对天然IV型胶原的活性。 观察到100-200 kDa以及18和22 kDa的纤连蛋白降解产物。 在非还原条件下从层粘连蛋白释放单个70 kDa片段，在还原条件下从45至200 kDa范围内的多个片段。 这些结果表明，组织蛋白酶B在恶性肿瘤细胞表面或附近可能发挥功能性作用，在局灶性溶解的细胞外基质。
Our laboratory has previously demonstrated that increased malignancy of several histological types of human and animal tumours is associated with increases in their cathepsin B activity, particularly cathepsin B activity associated with plasma-membrane/endosomal vesicles or shed vesicles. Here we report that cathepsin B from normal or tumour tissues degrades purified extracellular-matrix components, type IV collagen, laminin and fibronectin, at both acid pH and neutral pH. The number and sizes of degradation products were analysed by SDS/PAGE. Cathepsin B from both sources exhibited similar activities towards, and similar patterns of cleavage of, the extracellular-matrix proteins. At neutral pH, cathepsin B from both sources appeared to undergo autodegradation, a process that was decreased in the presence of alternative substrates such as the extracellular-matrix proteins. Cathepsin B readily degraded type IV collagen at 25-degrees-C, indicating activity towards native type IV collagen. Fibronectin degradation products of 100-200 kDa and of 18 and 22 kDa were observed. A single 70 kDa fragment was released from laminin under non-reducing conditions and multiple fragments ranging from 45 to 200 kDa under reducing conditions. These results suggest that cathepsin B at or near the surface of malignant tumour cells may play a functional role in the focal dissolution of extracellular matrices.