Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer.
Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer.
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DOI：
10.1186/1471-2407-6-211
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发表时间：
2006-08-18
期刊：
影响因子：
3.8
通讯作者：
Yoon WH
中科院分区：
文献类型：
--
作者：
Kim TD;Song KS;Li G;Choi H;Park HD;Lim K;Hwang BD;Yoon WH
基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和尿激酶型纤溶酶原激活物（uPA）参与结直肠癌的侵袭和转移。MMP-2和MMP-9的活性在结肠和直肠肿瘤之间是否存在差异仍有争议。本研究旨在探讨结直肠癌组织中MMP-2、MMP-9和uPA系统表达的差异。从结肠癌（n = 12）和直肠癌（n = 10）获得癌组织样品。MMP-2和MMP-9水平采用明胶酶谱法和Western印迹法检测，其内源性抑制剂，金属蛋白酶组织抑制剂-2（TIMP-2）和金属蛋白酶组织抑制剂-1（TIMP-1），通过Western印迹法进行评估。采用酶联免疫吸附试验（ELISA）检测uPA、uPAR和派-1。用酪蛋白-纤溶酶原酶谱法测定uPA活性。结直肠肿瘤组织中MMP-2、MMP-9和TIMP-1蛋白表达均高于相应配对的正常黏膜组织，而TIMP-2蛋白表达明显低于正常黏膜组织。MMP-2、MMP-9及其内源性抑制剂的酶活性或蛋白水平在结肠癌和直肠癌与其正常粘膜相比没有达到统计学显著差异。直肠癌组织中uPA活性高于结肠癌组织（P = 0.0266），而尿激酶型纤溶酶原激活物受体（uPAR）和纤溶酶原激活物抑制剂-1（派-1）在结肠癌和直肠癌组织中无显著性差异。这些结果表明，uPA可能在结肠癌和直肠癌中差异表达，然而，MMP-2、MMP-9、TIMP-1、TIMP-2、派-1和uPAR的活性或蛋白水平不受结肠或直肠中肿瘤位置的影响。
Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum.
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