Scully S P, Berend K R, Toth A, Qi W N, Qi Z, Block J A
Laboratory of Cell and Molecular Biology, Duke University Medical Center, Durham, NC 27710, USA.
Clin Orthop Relat Res. 2000 Jul(376):291-303. doi: 10.1097/00003086-200007000-00038.
Matrix metalloproteinases contribute to the processes of local invasion and metastasis by providing cells with the ability to traverse tissue boundaries. The levels of gene expression were quantitated for matrix metalloproteinases-1 and tissue inhibitors of metalloproteinases-1 in human chondrosarcoma cell lines, and the results were correlated with cell differentiation, collagenase activity, and in vitro invasion. Three well characterized human cell lines were used in this study, with the level of chondrocytic differentiation confirmed to be JJ012, FS090, and 105KC in increasing order on the basis of aggrecan and collagen gene expression. The matrix metalloproteinases-1/tissue inhibitors of metalloproteinases-1 ratio correlated with the level of differentiation in an inverse fashion. Collagenase activity paralleled matrix metalloproteinases-1/tissue inhibitors of metalloproteinases-1 gene expression and was associated with a more invasive phenotype in an in vitro assay. In this report, matrix metalloproteinase-1 and tissue inhibitors of metalloproteinases-1 expression in human chondrosarcoma tumor cell lines were quantitated, and it was shown that interstitial collagenase gene expression correlates inversely with chondrocytic differentiation. Differences in collagenase activity and in vitro invasion correlate inversely with the level of differentiation. These findings are consistent with the hypothesis that collagenase activity is associated with a poorer prognosis in chondrosarcoma by facilitating cell egress from the tumor matrix.
基质金属蛋白酶通过赋予细胞穿越组织边界的能力，促进局部侵袭和转移过程。对人软骨肉瘤细胞系中的基质金属蛋白酶-1和金属蛋白酶组织抑制剂-1的基因表达水平进行了定量分析，结果与细胞分化、胶原酶活性及体外侵袭相关。本研究使用了三种特征明确的人细胞系，根据聚集蛋白聚糖和胶原基因表达情况，确认软骨细胞分化水平依次为JJ012、FS090和105KC，且呈递增趋势。基质金属蛋白酶-1/金属蛋白酶组织抑制剂-1的比值与分化水平呈负相关。胶原酶活性与基质金属蛋白酶-1/金属蛋白酶组织抑制剂-1基因表达平行，且在体外实验中与更具侵袭性的表型相关。在本报告中，对人软骨肉瘤肿瘤细胞系中的基质金属蛋白酶-1和金属蛋白酶组织抑制剂-1表达进行了定量分析，结果表明间质胶原酶基因表达与软骨细胞分化呈负相关。胶原酶活性和体外侵袭的差异与分化水平呈负相关。这些发现与以下假设一致，即胶原酶活性通过促进细胞从肿瘤基质中逸出，与软骨肉瘤的预后较差相关。
