Matrix metalloproteinases in human melanoma
Matrix metalloproteinases in human melanoma
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DOI：
10.1046/j.1523-1747.2000.00068.x
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发表时间：
2000-09-01
影响因子：
6.5
通讯作者：
Ruiter, DJ
中科院分区：
文献类型：
--
作者：
Hofmann, UB;Westphal, JR;Ruiter, DJ
皮肤黑色素瘤是一种高度侵袭性和转移性的肿瘤。基底膜和细胞外基质的降解是黑色素瘤细胞迁移、侵袭和转移形成的重要步骤。基质金属蛋白酶及其组织抑制物在这些复杂的多步骤过程中起着至关重要的作用。黑色素瘤细胞可表达多种基质金属蛋白酶家族成员(MMP1、MMP2、MMP9、MMP13和MT1-MMP3)及其组织抑制因子(TIMP-1、TIMP-2和TIMP-3)。许多研究已经检测了基质金属蛋白酶及其组织抑制物，以及在体外和体内黑色素瘤细胞系以及人类黑素细胞病变中调节其表达和/或激活的分子。最近的研究结果表明，CD44和整合素α(V)β(3)等黏附分子参与了侵袭性肿瘤细胞表面活化的基质金属蛋白酶分子的定位。在这篇综述中，我们评估了基质金属蛋白酶及其组织抑制物在黑色素瘤进展中的作用的这些新的方面。我们认为，活化的基质金属蛋白酶及其组织抑制物的表达水平之间的平衡，以及活化的基质金属蛋白酶和黏附分子的共同表达是决定黑色素瘤细胞侵袭、肿瘤生长和转移形成的重要因素。
Cutaneous melanoma is a highly invasive and metastatic tumor. Degradation of basement membranes and extracellular matrix is an essential step in melanoma cell migration, invasion, and metastasis formation. Matrix metalloproteinases and their tissue inhibitors play a crucial role in these complex multistep processes. Melanoma cells may express a number of matrix metalloproteinase family members (MMP-1, MMP-2, MMP-9, MMP-13, and MT1-MMP) as well as their tissue inhibitors (TIMP-1, TIMP-2, and TIMP-3). Numerous studies have examined matrix metalloproteinases, their tissue inhibitors, and the molecules that regulate their expression and/or activation in melanoma cell lines in vitro and in vivo, and in human melanocytic lesions. Recent results have indicated that adhesion molecutes such as CD44 and integrin alpha(v)beta(3) are involved in positioning activated matrix metalloproteinase molecules on the cell surface of invasive tumor cells. In this review we evaluate these novel aspects of the role of matrix metalloproteinases and their tissue inhibitors in melanoma progression. We conclude that the balance between levels of activated matrix metalloproteinases and expression levels of their tissue inhibitors, and the coexpression of activated matrix metalloproteinases and adhesion molecules are important factors in determining melanoma cell invasion, tumor growth, and metastasis formation.