Increased matrix metalloproteinase 2 concentration and transcript expression in advanced colorectal carcinomas
Increased matrix metalloproteinase 2 concentration and transcript expression in advanced colorectal carcinomas
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DOI：
10.1007/s003840100287
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发表时间：
2001-06-01
影响因子：
2.8
通讯作者：
Stallmach, A
中科院分区：
文献类型：
--
作者：
Chan, CC;Menges, M;Stallmach, A
结直肠癌是最常见的恶性肿瘤之一，预后相对较差。临床结果取决于局部和转移性肿瘤扩散的程度。体内和体外研究的结果表明，基质金属蛋白酶（MMPs）和它们的抑制剂（金属蛋白酶组织抑制剂TIMPs）之间的平衡在肿瘤形成中被改变，有助于恶性肿瘤的侵袭和转移特性。我们定量的MMP-2和TIMP-2的组织浓度在65个恶性结直肠病变和相应的正常粘膜酶联免疫吸附试验，蛋白质印迹和原位杂交。原位杂交和蛋白质印迹分析表明，MMP-2的转录本和蛋白质在原发癌的基质表达明显增加。MMP-2的蛋白浓度在所有的肿瘤阶段，除了第一阶段的肿瘤，高于正常粘膜和腺瘤。MMP-2浓度与肿瘤分化或结肠与直肠位置无关。令人惊讶的是，MMP-2浓度在转移中没有增加。有趣的是，TIMP-2的组织浓度和上皮mRNA表达在原发性结直肠癌（UICC III期和IV期）中显著降低，但在转移灶中增加。因此，MMP-2与TIMP-2的比率增加与晚期肿瘤阶段密切相关，但在转移中观察到比率降低。这些结果表明，MMP-2：TIMP-2的比例可能被证明是有用的局部浸润标记，但不是转移结直肠癌。
Colorectal cancer is one of the most common malignant tumors and entails a relatively poor prognosis. Clinical outcome depends on the extent of local and metastatic tumor spread. Results of in vivo and in vitro studies suggest that the balance between matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases TIMPs) is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumors. We quantified tissue concentrations of MMP-2 and TIMP-2 in 65 malignant colorectal lesions and corresponding normal mucosa by enzyme-linked immunosorbent assay, western blotting, and in situ hybridization. In situ hybridization and western blot analyses demonstrated a clear increase in both stromal expression of MMP-2 transcripts and protein in primary carcinomas. The protein concentration of MMP-2 was higher in all tumor stages, except stage I tumors, than in normal mucosa and adenomas. MMP-2 concentrations were not related to tumor differentiation or to colonic versus rectal location. Surprisingly, the MMP-2 concentration was not increased in metastases. Interestingly, tissue concentrations and epithelial mRNA expression of TIMP-2 decreased significantly in primary colorectal cancer (UICC stages III and IV) but increased in metastases. Therefore an increased ratio of MMP-2 to TIMP-2 is strongly associated with advanced tumor stages, but a decreased ratio was observed in metastases. These findings suggest that the MMP-2:TIMP-2 ratio may prove useful as a marker of local invasion but not of metastasis in colorectal cancer.