Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.
Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.
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发表时间：
2001-08
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通讯作者：
B. Schmalfeldt;D. Prechtel;Kathrin Härting;K. Späthe;S. Rutke;Elisabeth Konik;R. Fridman;U. Berger;M. Schmitt;W. Kuhn;E. Lengyel
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作者：
B. Schmalfeldt;D. Prechtel;Kathrin Härting;K. Späthe;S. Rutke;Elisabeth Konik;R. Fridman;U. Berger;M. Schmitt;W. Kuhn;E. Lengyel
蛋白酶与不同实体瘤的恶性表型有关。因此，我们研究了基质金属蛋白酶（MMP）-2和MMP-9以及丝氨酸蛋白酶尿激酶型纤溶酶原激活剂（uPA）及其抑制剂纤溶酶原激活剂抑制剂1型（PAI-1）在卵巢癌进展中的表达。通过定量明胶酶谱和蛋白质印迹分析了 19 例囊腺瘤和 18 例低度恶性潜能 (LMP) 肿瘤以及 41 例国际妇产科联盟 IIIc/IV 期晚期卵巢癌原发肿瘤及其相应大网膜转移瘤的组织提取物中 MMP-2 和 MMP-9 的明胶分解活性和蛋白表达。在相同的组织提取物中，通过 ELISA 测定 uPA 及其抑制剂 PAI-1 的抗原水平。 pro-MMP-2 (72 kDa) 和 pro-MMP-9 (92 kDa) 蛋白表达以及 uPA 和 PAI-1 抗原水平在良性卵巢肿瘤中较低，但从 LMP 肿瘤到晚期卵巢癌显着增加。所有蛋白水解因子的最高值在网膜转移中检测到。活性 MMP-2 酶 (62 kDa) 仅在 卵巢癌 (66%) 和相应的转移瘤 (93%)，但从未出现在良性或 LMP 肿瘤中。转移灶中 MMP-2 对其活性亚型的激活率较高。比较两种蛋白水解系统，在 pro-MMP-9 表达较高的癌症中始终发现较高的 PAI-1 浓度。这些数据表明纤溶酶原激活剂系统的成员以及金属蛋白酶 MMP-2/9，随着卵巢肿瘤恶性潜能的增加而增加。这些发现与蛋白酶抑制剂作为卵巢癌新治疗方法的开发特别相关。
Proteases are linked to the malignant phenotype of different solid tumors. Therefore, the expression of the matrix metalloproteinase (MMP)-2 and MMP-9 and of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) in the progression of ovarian cancer was investigated. Gelatinolytic activity and protein expression of MMP-2 and MMP-9 were analyzed in tissue extracts of 19 cystadenomas and 18 low malignant potential (LMP) tumors, as well as 41 primary tumors of advanced ovarian cancer stage International Federation of Gynecology and Obstetrics IIIc/IV and their corresponding omentum metastases by quantitative gelatin zymography and Western blot. In the same tissue extracts, antigen levels of uPA and its inhibitor PAI-1 were determined by ELISA. Protein expression of pro-MMP-2 (72 kDa) and pro-MMP-9 (92 kDa as well as antigen levels of uPA and PAI-1 were low in benign ovarian tumors but increased significantly from LMP tumors to advanced ovarian cancers. The highest values of all of the proteolytic factors were detected in omentum metastases. Active MMP-2 enzyme (62 kDa) was detected only in ovarian cancer (66%) and corresponding metastases (93%) but never in benign or LMP tumors. The activation rate of MMP-2 to its active isoform was higher in the metastases. Comparing both proteolytic systems, higher PAI-1 concentrations were consistently found in cancers with high pro-MMP-9 expression. These data indicate that members of the plasminogen activator system, as well as the metalloproteinases MMP-2/9, increase with growing malignant potential of ovarian tumors. These findings are of particular relevance to the development of protease inhibitors as new therapeutic approaches in ovarian cancer.