Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen
Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen
复制标题
DOI：
10.1074/jbc.m010053200
复制
发表时间：
2001-06-01
影响因子：
4.8
通讯作者：
McCarthy, JB
中科院分区：
文献类型：
--
作者：
Iida, J;Pei, D;McCarthy, JB
肿瘤细胞的粘附和细胞外基质蛋白的降解是肿瘤侵袭过程中紧密相连的过程。在这项研究中，我们试图确定组件的垂直生长期黑色素瘤细胞系，WM 1341 D，介导的侵入性细胞行为的细胞表面。我们确定的反义抑制，黑色素瘤硫酸软骨素蛋白聚糖（MCSP）和膜型3基质金属蛋白酶（MT3-MMP）的WM 1341 D上表达的I型胶原蛋白的侵袭和I型明胶的降解所需的。在以I型胶原或层粘连蛋白为基质的WM 1341 D黑色素瘤细胞中，MT3-MMP与MCSP共沉淀，通过从细胞表面去除硫酸软骨素糖胺聚糖（CS），MT3-MMP与MCSP之间的结合被极大地破坏，表明CS可以介导两种细胞表面核心蛋白之间的结合。重组MT3-MMP和来自WM 1341 D细胞的全细胞裂解物的MT3-MMP从CS缀合的亲和柱特异性洗脱。结果表明，MT3-MMP具有促进黑色素瘤侵袭和蛋白水解的潜力，MT3-MMP和MCSP之间形成复合物可能是激活这些过程的关键步骤。
Tumor cell adhesion and proteolysis of the extracellular matrix proteins surrounding the cells are tightly linked processes in tumor invasion. In this study, we sought to identify components of the cell surface of a vertical growth phase melanoma cell line, WM1341D, that mediate invasive cellular behavior. We determined by antisense inhibition that melanoma chondroitin sulfate proteoglycan (MCSP) and membrane-type 3 matrix metalloproteinase (MT3-MMP) expressed on WM1341D are required for invasion of type I collagen and degradation of type I gelatin. MT3-MMP co-immunoprecipitated with MCSP in WM1341D melanoma cells cultured on type I collagen or laminin, The association between MT3-MMP and MCSP was largely disrupted by removing chondroitin sulfate glycosaminoglycan (CS) from the cell surface, suggesting CS could mediate the association between the two cell surface core proteins. Recombinant MT3-MMP and MT3-MMP from whole cell lysates of WM1341D cells were specifically eluted from CS-conjugated affinity columns. The results indicate that MT3-MMP possesses the potential to promote melanoma invasion and proteolysis and that the formation of a complex between MT3-MMP and MCSP may be a crucial step in activating these processes.