Otani Y, Fujii M, Kubota T, Kitajima M, Okada Y
Dept. of Surgery, School of Medicine, Keio University, Japan.
Gan To Kagaku Ryoho. 1998 Jun;25(7):957-64.
The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc-endopeptidases. These enzymes are capable of degrading the extracellular matrix, including collagens, laminin, proteoglycan and fibronectin. In some human cancers, a positive correlation has been demonstrated between MMP expression and the likelihood of developing metastasis. An imbalance between MMPs and the tissues inhibitor of metalloproteinases (TIMPs) may play a significant role in the invasive phenotype of cancers. Although TIMPs have been shown to inhibit tumor metastasis in some in vivo models, they are not suitable for pharmacologic applications due to their short half-life in vivo and large molecular size. In this paper, recent advances in MMP research and reports of clinical applications of synthetic MMP inhibitors for cancer patients are reviewed.
基质金属蛋白酶(MMPs)是一类分泌型和膜结合型锌内肽酶。这些酶能够降解细胞外基质,包括胶原蛋白、层粘连蛋白、蛋白聚糖和纤连蛋白。在一些人类癌症中,MMP表达与发生转移的可能性之间已显示出正相关。MMPs与金属蛋白酶组织抑制剂(TIMPs)之间的失衡可能在癌症的侵袭表型中起重要作用。尽管在一些体内模型中已表明TIMPs可抑制肿瘤转移,但由于它们在体内的半衰期短且分子量大,因此不适合用于药物应用。本文综述了MMP研究的最新进展以及合成MMP抑制剂在癌症患者中的临床应用报告。