HUMAN COLLAGENASE IV AND ITS INHIBITORS

基底膜中IV型胶原蛋白网络的降解是一种 在许多正常和病理条件下，包括组织 重塑、伤口愈合、肿瘤细胞转移和血管生成。 的 72 Kd IV型胶原酶是一种中性金属蛋白酶，能够降解 IV型胶原与恶性肿瘤的发生有关， 细胞转移和血管生成的过程中。 天然 已知为TIMP-2的72 kD酶的存在抑制剂（组织抑制剂 金属蛋白酶-2）与72 kD IV型形成非共价复合物 前胶原酶并特异性抑制其酶活性。 TIMP-2 是制定新战略的潜在候选者， 治疗转移和血管生成疾病。 我们打算生产 毫克量的生物活性TIMP-2和72 kD IV型 重组DNA技术制备胶原酶并对其进行表征 生物化学和生物学特性。 这些蛋白质的可用性将 使我们能够研究它们在疾病中的作用，并开发抗体， 用于免疫诊断和治疗癌症的特定药物。

The degradation of the collagen type IV network in basement membranes is a critical event in many normal and pathological conditions including tissue remodelling, wound healing, tumor cell metastasis, and angiogenesis. The 72 Kd type IV collagenase is a neutral metalloprotease capable of degrading collagen type IV that has been implicated in the ability of malignant tumor cells to metastasize and in the process of angiogenesis. A naturally occurring inhibitor of the 72 kD enzyme known as TIMP-2 (tissue inhibitor of metalloprotease-2) form a noncovalent complex with the 72 kD type IV procollagenase and specifically inhibits its enzyme activity. Thus, TIMP-2 is a potential candidate for the development of new strategies for the treatment of metastasis and angiogenic diseases. We intend to produce milligram quantities of biologically active TIMP-2 and 72 kD type IV collagenase by recombinant DNA technology and characterize their biochemical and biological properties. Availability of these proteins will allow us to study their role in disease and to develop antibodies and specific drugs to be used in immunodiagnostic and treatment of cancer.