Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.
Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura.
复制标题
DOI：
10.1038/sj.bjc.6600920
复制
发表时间：
2003-05-19
影响因子：
8.8
通讯作者：
O'Byrne, K J
中科院分区：
文献类型：
--
作者：
Edwards, J G;McLaren, J;Jones, J L;Waller, D A;O'Byrne, K J
基质金属蛋白酶(MMPs)，尤其是明胶酶(MMP2和MMP9)在肿瘤侵袭和血管生成中起重要作用。在恶性间皮瘤(MM)肿瘤样本中，MMPs的表达和活性尚未被表征。在一项前瞻性研究中，用半定量明胶酶谱检测了冷冻MM(n=35)、炎症胸膜(IP，n=12)和非炎症胸膜(UP，n=14)组织匀浆上清液中明胶酶的活性。采用Kaplan-Meier和Cox比例风险模型分析了基质金属蛋白酶与临床病理因素和生存期的关系。MM组织中MMP2的表达水平明显高于MMP9的表达水平(P=0.006，P<0.001)。MM组MMP2活性显著高于UP组(P=0.04)。IP组和MM组的MMP2活性相当，但活性高于IP组(P=0.02，P=0.009)。在单因素分析中，随着总活性和原-MMP2活性的增加，患者的生存率有下降趋势(P=0.08)，但在多因素分析中，随着体重减轻，两者都是独立的预后不良因素(原-MMP2活性P=0.03，总MMP2活性P=0.04)。总的和前-基质金属蛋白酶-2也有助于癌症和白血病B组的预后。基质金属蛋白酶-9活性不能预测预后。基质金属蛋白酶，尤其是最丰富的明胶酶-2，可能在MM肿瘤的生长和转移中起重要作用。减少基质金属蛋白酶合成和/或活性的药物可能在MM的管理中发挥作用。
Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n=35), inflamed pleura (IP, n=12) and uninflammed pleura (UP, n=14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan–Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 (P=0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP (P=0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP (P=0.02, P=0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P=0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P=0.03, total MMP-2 P=0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM.