CATHEPSIN B-LIKE CYSTEINE PROTEINASES AND TUMOR INVASION

蛋白水解酶与蛋白质的溶解有关 细胞外基质在肿瘤细胞进入其他组织的过程中 转移性级联。一种蛋白水解酶，已经被 与转移能力相关的是组织蛋白酶B或组织蛋白酶B样蛋白 半胱氨酸蛋白酶(CB)。我们正在研究CB在肿瘤中的作用 从正常肝脏和几种肿瘤中分离酶进行转移 人类和老鼠的血型。它的物理和动力学性质 人们正在将肿瘤酶与正常肝脏中的组织蛋白酶B进行比较 在我们实验室中分离出来并发表了关于组织蛋白酶B的观察结果 从几个正常组织中分离出来。我们现在已经证明了肿瘤 尤其是转移性肿瘤的CB与血浆有关。 膜以及与溶酶体的结合。在进一步的研究中，我们计划 分离和鉴定与质膜相关的CB。精制炭黑 酶正在并将被用于开发多克隆和 单克隆抗体。纯化的酶和抗体将是 用于细胞外消化后侵袭的体外研究 基质成分与肿瘤细胞在人羊膜基底中的运动 薄膜。这些研究应该会加深我们对潜在作用的了解 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)