Mochizuki Satsuki, Okada Yasunori
Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.
Cancer Sci. 2007 May;98(5):621-8. doi: 10.1111/j.1349-7006.2007.00434.x. Epub 2007 Mar 9.
A disintegrin and metalloproteinases (ADAMs) are a new gene family of proteins with sequence similarity to the reprolysin family of snake venomases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). They are structurally classified into two groups: the membrane-anchored ADAM and ADAM with thrombospondin motifs (ADAMTS). These molecules are involved in various biological events such as cell adhesion, cell fusion, cell migration, membrane protein shedding and proteolysis. Studies on the biochemical characteristics and biological functions of ADAMs are in progress, and accumulated lines of evidence have shown that some ADAMs are expressed in malignant tumors and participate in the pathology of cancers. The activities of ADAMs are regulated by gene expression, intracytoplasmic and pericellular regulation, activation of the zymogens and inhibition of activities by inhibitors. Many ADAM species, including ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19, ADAM28, ADAMTS1, ADAMTS4 and ADAMTS5, are expressed in human malignant tumors. Many of them are involved in the regulation of growth factor activities and integrin functions, leading to promotion of cell growth and invasion, although the precise mechanisms of these are not clear at the present time. In this article, we review recent information about ADAM family members and their implications for cancer cell proliferation and progression.
解整合素金属蛋白酶（ADAMs）是一个新的蛋白质基因家族，其序列与蛇毒溶解素家族的解聚素相似，与基质金属蛋白酶（MMPs）共享金属蛋白酶结构域。它们在结构上分为两组：膜锚定ADAM和具有血小板反应蛋白基序的ADAM（ADAMTS）。这些分子参与各种生物学事件，如细胞粘附、细胞融合、细胞迁移、膜蛋白脱落和蛋白水解。对ADAMs的生化特性和生物学功能的研究正在进行中，越来越多的证据表明，一些ADAMs在恶性肿瘤中表达并参与癌症的病理过程。ADAMs的活性受基因表达、胞浆内和细胞周围调节、酶原激活以及抑制剂对活性的抑制作用的调控。许多ADAM家族成员，包括ADAM8、ADAM9、ADAM10、ADAM12、ADAM15、ADAM17、ADAM19、ADAM28、ADAMTS1、ADAMTS4和ADAMTS5，在人类恶性肿瘤中表达。其中许多参与生长因子活性和整合素功能的调节，导致细胞生长和侵袭的促进，尽管目前其确切机制尚不清楚。在本文中，我们综述了有关ADAM家族成员的最新信息及其对癌细胞增殖和进展的影响。
