Evaluation of MMP inhibitors for cancer treatment

基质金属蛋白酶(MMPs)降解细胞外基质(ECM)，支持癌细胞在组织中的侵袭，最终形成转移。抑制基质金属蛋白酶活性有望阻止癌细胞生长、侵袭和转移，以及血管生成。在MMPs中，膜型MMPs(MT-MMPs)被认为对癌细胞的侵袭很重要，因为它们负责细胞在组织中穿行所需的细胞外基质的周围性降解。到目前为止，已知五种MT-MMP。其中一种是MT1-MMPs，在癌细胞中频繁表达，并激活明胶酶原A，能够降解基底膜中的IV型胶原。(1)MT1-MMPs的定位通过与细胞内的肌动蛋白结合来调节。(2)为了在亚细胞水平检测MT-MMPs的活性，我们建立了一种检测体系，可以用FITC包被的明胶膜或DQ-明胶来激活它们的荧光素。(3)利用大肠杆菌表达系统成功地制备了具有催化活性的MT1、MT2、MT3、MT4和MT5-MMPs。

Matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) and support cancer cell invasion in tissue, and eventually metastasis formation. Inhibition of MMP activity is expected to prevent cancer cell growth, invasion and metastasis, and angiogenesis. Among the MMPs, membrane-type MMPs (MT-MMPs) are thought to be important for cancer cell invasiohbecause that are responsible for perice11ular degradation of ECM that is required for cells to traverse in tissue. So far five MT-MMPs are known. One of them, MT1-MMP, is frequently expressed in cancer cells and activates pro-gelatinase A which is able to degrade type IV collagen in the basement membrane.(1) Localization of MT1-MMP was found to be regulated by associating with actin cytoskelton within the cells.(2) To detect MT-MMP activities at subcellular level, we established an assay system by using either FITC-coated gelatin film or DQ-gelatin of which fuluorecense can be activated by proteolytic cleavage.(3) Preparation of catalitically active MT1, MT2, MT3, MT4 and MT5-MMPs were successful by using an expression system in E. coli.