BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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.

译文

背景: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剂(uPA)参与大肠癌的侵袭和转移。尚存在关于结肠和直肠肿瘤之间MMP-2和MMP-9活性是否不同的争论。我们设计了这项研究,以确定结肠和直肠癌组织之间MMP-2,MMP-9和uPA系统表达的任何差异。
方法:从结肠癌(n = 12)和直肠癌(n = 10)中获得癌组织样本。使用明胶酶谱法和蛋白质印迹法检测MMP-2和MMP-9水平。通过蛋白质印迹法评估了它们的内源性抑制剂金属蛋白酶2的组织抑制剂(TIMP-2)和金属蛋白酶1的组织抑制剂(TIMP-1)。使用酶联免疫吸附测定(ELISA)检测uPA,uPA​​R和PAI-1。通过酪蛋白-纤溶酶原酶谱法评估uPA的活性。
结果:在结肠和直肠肿瘤中,MMP-2,MMP-9和TIMP-1蛋白水平均高于相应的配对正常黏膜,而TIMP-2水平显着低于正常黏膜。与正常黏膜相比,结肠癌和直肠癌中MMP-2,MMP-9及其内源性抑制剂的酶活性或蛋白质水平没有统计学上的显着差异。在直肠肿瘤中,与结肠肿瘤相比,uPA活性增加(P = 0.0266),但是尿激酶型纤溶酶原激活物受体(uPAR)和纤溶酶原激活物抑制物-1(PAI-1)之间没有显着差异。结肠和直肠癌组织。
结论:这些发现表明uPA在结肠癌和直肠癌中可能表达不同,但是,MMP-2,MMP-9,TIMP-1,TIMP-2,PAI-1和uPAR的活性或蛋白水平不受以下因素的影响肿瘤在结肠或直肠中的位置。

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