Arkona C, Wiederanders B
Institute of Biochemistry, Medical Faculty, Friedrich-Schiller-University, Jena, Germany.
Biol Chem. 1996 Nov;377(11):695-702. doi: 10.1515/bchm3.1996.377.11.695.
The possible application of proteinase inhibitors in the support of anti-tumor chemotherapy requires profound knowledge of the proteinases involved in malignant processes. Therefore, the occurrence of cathepsins B, D, H, L and S and of gelatinases, urokinase plasminogen activator and stromelysins was studied in biopsies of aggressive human bone metastases, of low invading basal cell carcinomas, and in normal placenta as control, by activity measurements and zymographic techniques. Cathepsin B and L, as well as gelatinase B, were shown to be overexpressed in bone metastases, suggesting a function during the metastatic process. Subcellular fractionation allowed detection of differential sorting of cathepsin B and gelatinases in metastatic tissue and also in normal human placenta. Plasma membrane binding could be demonstrated for both cathepsin B and gelatinase B. Whereas cathepsin B is at least partially bound to plasma membranes via alpha 2-macroglobulin and its LRP/alpha 2-macroglobulin receptor, gelatinase B binds to plasma membranes by an unknown mechanism.
蛋白酶抑制剂在抗肿瘤化疗支持中的潜在应用需要深入了解参与恶性过程的蛋白酶。因此，通过活性测量和酶谱技术，研究了组织蛋白酶B、D、H、L和S、明胶酶、尿激酶型纤溶酶原激活剂和基质溶解素在侵袭性人类骨转移活检组织、低侵袭性基底细胞癌组织以及作为对照的正常胎盘中的存在情况。结果显示，组织蛋白酶B和L以及明胶酶B在骨转移组织中过表达，提示它们在转移过程中发挥作用。亚细胞分级分离可检测到组织蛋白酶B和明胶酶在转移组织以及正常人类胎盘中的差异分选。已证实组织蛋白酶B和明胶酶B均与质膜结合。组织蛋白酶B至少部分通过α2-巨球蛋白及其LRP/α2-巨球蛋白受体与质膜结合，而明胶酶B通过未知机制与质膜结合。
