Pesta M, Holubec L, Topolcan O, Cerna M, Rupert K, Holubec L Sen, Treska V, Kormunda S, Elgrova L, Finek J, Cerny R
Central Laboratory of Radioisotopes, Charles University and Faculty Hospital, Pilsen, Czech Republic.
Anticancer Res. 2005 Sep-Oct;25(5):3387-91.
An essential step in the process of tumor invasion and metastasis involves the degradation of tissue barriers in the extracellular matrix (ECM), particularly in the basal membrane (BM). Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), in particular MMP-2, MMP-7, TIMP-1 and TIMP-2, play an important role in the process of ECM and BM degradation in connection with tumor invasion. The aim of our study was to assess the levels of MMP-2, MMP-7, TIMP-1 and TIMP-2 mRNA expression in colorectal carcinoma tissue samples and to correlate them with the stage of the disease.
The study included samples of tumor tissue of 38 patients with colorectal carcinoma and samples of tissue of 11 patients with benign disease. The expression levels of mRNA MMP-2, MMP-7, TIMP-1, TIMP-2 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as housekeeping gene, were quantified in tissue samples using the method of reverse transcription real-time PCR.
The levels of mRNA expression of MMP-2, MMP-7 and TIMP-1 were significantly higher in tumor tissue samples that in the control tissue (p<0.0005, p<0.0007 and p<0.0004). In addition the presence of mRNA MMP-2, MMP-7, TIMP-1 and TIMP-2 in tumor tissue samples in these parameters was significantly higher than in the control tissue (p<0.003, p<0.0001, p<0.0001 and p<0.05).
This pilot study demonstrated that a significant difference in the level and in the presence of mRNA MMP-2, MMP-7 and TIMP-1 expressions between tumor colorectal and control colorectal tissues might be helpful for the prognosis of colorectal cancer.
肿瘤侵袭和转移过程中的一个关键步骤涉及细胞外基质(ECM)中组织屏障的降解,尤其是基底膜(BM)。基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制剂(TIMPs),特别是MMP - 2、MMP - 7、TIMP - 1和TIMP - 2,在与肿瘤侵袭相关的ECM和BM降解过程中发挥重要作用。我们研究的目的是评估结直肠癌组织样本中MMP - 2、MMP - 7、TIMP - 1和TIMP - 2 mRNA的表达水平,并将其与疾病分期相关联。
该研究包括38例结直肠癌患者的肿瘤组织样本和11例良性疾病患者的组织样本。使用逆转录实时PCR方法对组织样本中MMP - 2、MMP - 7、TIMP - 1、TIMP - 2和作为管家基因的甘油醛 - 3 - 磷酸脱氢酶(GAPDH)的mRNA表达水平进行定量。
肿瘤组织样本中MMP - 2、MMP - 7和TIMP - 1的mRNA表达水平显著高于对照组织(p < 0.0005、p < 0.0007和p < 0.0004)。此外,在这些参数方面,肿瘤组织样本中MMP - 2、MMP - 7、TIMP - 1和TIMP - 2的mRNA存在水平显著高于对照组织(p < 0.003、p < 0.0001、p < 0.0001和p < 0.05)。
这项初步研究表明,结直肠癌肿瘤组织与对照结直肠组织之间MMP - 2、MMP - 7和TIMP - 1 mRNA表达水平及存在情况的显著差异可能有助于结直肠癌的预后评估。