基质金属蛋白酶和组织金属蛋白酶抑制剂在大肠癌中的表达

目的　研究基质金属蛋白酶 (MMPs)及组织金属蛋白酶抑制剂 (TIMPs)在大肠癌中的表达特点 ,与肿瘤发生发展的关系 ,以及在肿瘤治疗中的应用前景。　方法　采用RT PCR方法测定 2 8例大肠癌患者肿瘤组织和周围正常粘膜的基质金属蛋白酶 2 (MMP 2 )、膜型 1 基质金属蛋白酶 (MT1 MMP)、基质溶素 (MMP 7)、组织金属蛋白酶抑制剂 2 (TIMP 2 )、组织金属蛋白酶抑制剂 3(TIMP 3)的mRNA表达状况 ,并将其结果与临床及病理学资料进行统计学分析。　结果　 (1) 2 7例患者肿瘤组织中MMP 7mRNA表达阳性 ,MMP 2、MT1 MMP、TIMP 2和TIMP 3在肿瘤组织和正常粘膜中均有高表达 ;(2 )肿瘤组织中MMP 7mRNA的表达水平与大肠癌患者的Dukes′分期相关 (P <0 0 1) ;(3)淋巴结阳性患者的肿瘤组织TIMP 2表达水平为 (1 2 5± 0 46 )明显高于淋巴结阴性患者的 (0 75± 0 41) ,差异有显著性意义 (P <0 0 1) ;(4)大肠癌患者癌周正常粘膜TIMP 3mRNA表达随患者Duke′s分期的进展和肿瘤浸润深度的增加而降低 (P <0 0 1) ;(5 )TIMPs与MMPs之间无明显相关关系 (P >0 1)。　结论　MMP 7可望成为诊断大肠癌的敏感指标 ;人工诱导TIMP 2、TIMP 3或阻断MMP 7、MMP 2、MT1 MMP的表达可能抑制肿瘤的浸润和转移 ,成为肿瘤治疗的新途径。

Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal neoplasm

OBJECTIVES: To explore the relationship of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) to the oncogenesis and development of colorectal neoplasm. METHODS: RT-PCR was used to assay the level of MMP-2, MT1-MMP, MMP-7, TIMP-2, TIMP-3 mRNA in 28 cases of colorectal cancer, including tumor tissue and surrounding normal tissue. RESULTS: MMP-2, MT1-MMP, TIMP-2 and TIMP-3 were over-expressed in tumor and normal tissues, and MMP-7 was strong-expressed in tumor tissue but was weak-expressed only in one case of normal tissue. The expression of MMP-7 in tumor tissue was correlated to Dukes stage (P < 0.01). The expression of TIMP-2 in tumor tissue with positive-node was much higher than that with negative-node (P < 0.01). The expression of TIMP-3 was decreased with the Dukes stage and the depth of invasion (P < 0.01). There were no correlations between MMPs and TIMPs (P > 0.1). CONCLUSIONS: The expression of MMP-7 mRNA has a high specificity in colorectal cancer. MMP-7 may become a sensitive tumor marker. Inducing TIMP-2, TIMP-3 or suppressing MMP-2, MT1-MMP, MMP-7 mRNA's expressions may inhibit the invasion and metastasis of cancer.