CATHEPSIN B-LIKE CYSTEINE PROTEINASES AND TUMOR INVASION

蛋白质水解酶已经被牵连在溶解的 细胞外基质作为肿瘤细胞移动到其他组织在 转移级联反应 蛋白水解酶之一 与转移能力相关的是组织蛋白酶B或组织蛋白酶B样 半胱氨酸蛋白酶（CB）。 我们正在研究CB在肿瘤中的作用 通过从正常肝脏和几种肿瘤中分离酶来转移 人类和老鼠的基因型 的物理和动力学性质 将肿瘤酶与正常肝脏的组织蛋白酶B进行比较 分离在我们的实验室和发表的观察组织蛋白酶B 从几种正常组织中分离出来 我们已经证明肿瘤 特别是转移性肿瘤具有与血浆相关的CB 膜以及与溶酶体。 在进一步的研究中，我们计划 分离并表征质膜相关CB。 纯化CB 酶正在并将用于开发多克隆和 克隆抗体 纯化的酶和抗体将被 用于消化细胞外基质后的体外侵袭研究 基质成分与肿瘤细胞在羊膜基底中的运动 膜的 这些研究应该进一步加深我们对 半胱氨酸蛋白酶在肿瘤转移中的作用 （B）

Proteolytic enzymes have been implicated in dissolution of the extracellular matrix as tumor cells move into other tissues during the metastatic cascade. One of the proteolytic enzymes that has been correlated with metastatic capability is cathepsin B or a cathepsin B-like cysteine proteinase (CB). We are studying the role of CB in tumor metastasis by isolating the enzyme from normal liver and several tumor types from both humans and mice. The physical and kinetic properties of the tumor enzymes are being compared to cathepsin B from normal liver isolated in our laboratory and to published observations on cathepsin B isolated from several normal tissues. We have now demonstrated that tumors and in particular metastatic tumors have CB associated with the plasma membrane as well as with the lysosomes. In further studies we plan to isolate and characterize the plasma membrane-associated CB. Purified CB enzymes are being and will be used for development of polyclonal and monoclonal antibodies. The purified enzymes and the antibodies will be used for in vitro studies of invasion following digestion of extracellular matrix components and movement of tumor cells through human amnion basement membrane. These studies should further our knowledge of the potential role of cysteine proteinases in tumor metastasis. (B)