Matrix metalloproteinase digestion of aggrecan in human cartilage tumours.
Matrix metalloproteinase digestion of aggrecan in human cartilage tumours.
复制标题
基质金属蛋白酶消化人软骨肿瘤中的聚集蛋白聚糖。
DOI：
10.1016/s0959-8049(98)00239-1
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Towle,CA
中科院分区：
文献类型：
--
作者：
Toriyama,M;Rosenberg,AE;Mankin,HJ;Fondren,T;Treadwell,BV;Towle,CA
大量的实验和临床证据表明，细胞外基质成分的催化是实体瘤侵袭和转移行为的先决条件。软骨肉瘤是最常见于骨中的恶性软骨肿瘤，并且大的聚集性蛋白聚糖聚集蛋白聚糖是这些肿瘤的细胞外基质的主要组分。基质金属蛋白酶（MMPs）与肿瘤的侵袭性有关。本研究的目的是确定MMPs是否在软骨肿瘤中的聚集蛋白聚糖催化中发挥作用。为了检测由MMP位点处的体内切割产生的聚集蛋白聚糖消化产物，使用针对由MMP切割产生的FVDIPEN新表位的抗体通过Western印迹分析来自人关节软骨和来自各种软骨肿瘤的蛋白质提取物。软骨提取物的检查揭示了随着年龄的增长在MMP位点增加聚集蛋白聚糖消化的趋势。一个透明软骨肉瘤和三个骨软骨瘤缺乏可检测的聚集蛋白聚糖片段与羧基末端FVDIPEN新表位。2例骨软骨瘤信号微弱。然而，所有软骨肉瘤细胞外基质退化或粘液成分表现出强烈的FVDIPEN免疫反应。这些结果表明，与良性软骨肿瘤骨软骨瘤相反，人软骨肉瘤含有丰富的聚集蛋白聚糖降解产物，这些降解产物是由体内球间结构域中MMP位点处的裂解产生的。这些数据支持这样的概念，即MMPs参与软骨肉瘤细胞外基质的降解，使肿瘤软骨细胞逃脱局部限制，迁移，并侵入邻近和远程组织。
Substantial experimental and clinical evidence suggests that the catabolism of extracellular matrix components is a prerequisite for invasive and metastatic behaviour of solid tumours. Chondrosarcomas are malignant cartilaginous tumours that most commonly arise in bone, and the large aggregating proteoglycan aggrecan is a major component of the extracellular matrix of these tumours. Matrix metalloproteinases (MMPs) have been implicated in tumour invasiveness. The purpose of this study was to determine whether MMPs play a role in aggrecan catabolism in cartilage tumours. In order to detect aggrecan digestion products resulting from in vivo cleavage at the MMP site, protein extracts from human articular cartilage and from various cartilage tumours were analysed by Western blot using an antibody to the FVDIPEN neoepitope generated by MMP cleavage. Examination of cartilage extracts revealed a trend of increasing aggrecan digestion at the MMP site with age. One hyaline chondrosarcoma and three osteochondromas lacked detectable aggrecan fragments with the carboxy terminal FVDIPEN neoepitope. Two osteochondromas gave weak signals. However, all chondrosarcomas with degenerating extracellular matrix or with a myxoid component exhibited strong FVDIPEN immunoreactivity. These results demonstrate that, in contrast to the benign cartilage tumour osteochondroma, human chondrosarcomas contain abundant aggrecan degradation products resulting from cleavage in vivo at the MMP site in the interglobular domain. These data support the concept that MMPs participate in the degradation of extracellular matrix in chondrosarcoma, allowing the neoplastic chondrocytes to escape local confinement, migrate, and invade neighbouring and remote tissues.