Kugler A, Hemmerlein B, Thelen P, Kallerhoff M, Radzun H J, Ringert R H
Department of Urology and Pathology, Georg-August-University, Göttingen, Germany.
J Urol. 1998 Nov;160(5):1914-8.
Degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and MMP-9, are supposed to be key enzymes in this process. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 RNA using reverse transcriptase PCR technique with tumor stage in 17 samples of renal cell carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing TIMP-1 and TIMP-2 was defined to be 1 in normal kidney tissue. This MMP:TIMP ratio was significantly increased to 2.43 (standard deviation, SD = 0.8) in locally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIMP expression was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma.
细胞外基质的降解是癌细胞侵袭和转移所必需的。两种明胶溶解基质金属蛋白酶，即基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9），被认为是这一过程中的关键酶。本研究的目的是采用逆转录聚合酶链反应技术，将MMP-2、MMP-9及其抑制剂与金属蛋白酶组织抑制剂TIMP-1和TIMP-2 RNA的存在情况，与17例肾细胞癌样本的肿瘤分期相关联。在正常肾组织中，表达MMP-2和MMP-9的组织与表达TIMP-1和TIMP-2的组织的比例定义为1。在局限性肾细胞癌中，这种MMP:TIMP比例显著增加至2.43（标准差，SD = 0.8），在晚期癌中增加至4.86（SD = 1.1）（p <0.01）。在原发性肿瘤细胞系中，MMP:TIMP表达比例为3.44（SD = 0.6）。这些数据表明，MMP-2和MMP-9与TIMP-1和TIMP-2表达的平衡是肾细胞癌侵袭性的一个重要因素。
