Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer
Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer
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DOI：
10.1136/jcp.55.10.758
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发表时间：
2002-10-01
影响因子：
3.4
通讯作者：
Murray, GI
中科院分区：
文献类型：
--
作者：
Leeman, MF;McKay, JA;Murray, GI
目的：基质金属蛋白酶(MMPs)是一类能降解所有细胞外基质成分，尤其是纤维状胶原的蛋白水解酶家族。这组蛋白在肿瘤侵袭和转移过程中的重要性现在得到了广泛的承认。基质金属蛋白酶-13(胶原酶3)在基质金属蛋白酶的活化级联反应中起核心作用。本研究的目的是探讨基质金属蛋白酶-13在结直肠癌中的表达及其与临床病理特征的关系。方法：对249例临床病理资料一致的结直肠癌石蜡包埋福尔马林固定切片进行免疫组织化学染色。使用DAKO TechMate(TM)500自动免疫染色系统，用抗基质金属蛋白酶-13的单抗检测对基质金属蛋白酶-13的免疫反应。使用半定量评分系统评估基质金属蛋白酶-13的存在和细胞定位。明胶酶谱法检测基质金属蛋白酶-13活性。对免疫组织化学研究的一组病例进行了酶谱分析，两组病例包括10对Dukes‘s C转移率和正常组织标本，按生存“好”或“差”进行选择。结果：91%的病例检测到对基质金属蛋白酶-13的免疫反应，免疫反应定位于肿瘤细胞的胞浆。基质金属蛋白酶-13染色评分越高，生存率越差。肿瘤的基质金属蛋白酶-13活性显著高于正常结肠粘膜(p<；0.001)。此外，生存不良组的转化率与正常组织的比率显著高于正常组织(p=0.02)。结论：本研究结果表明，在结直肠癌中，基质金属蛋白酶-13的表达频繁且活跃，提示基质金属蛋白酶-13的活性与结直肠癌的不良生存有关。
Aims: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes collectively capable of degrading all extracellular matrix components, in particular fibrillar collagen. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged. MMP-13 (collagenase 3) has a central role in the MMP activation cascade. The purpose of this study was to investigate the presence and activity of MMP-13 in colorectal cancer and relate these to clinicopathological features.Methods: Immunohistochemistry for MMP-1 3 was performed on formalin fixed, paraffin wax embedded sections of a large series of colorectal cancers (n = 249), all of which had uniform clinical and pathological information available. Immunoreactivity to MMP-13 was detected with a monoclonal antibody to MMP-13 using a Dako TechMate(TM)500 automated immunostaining system. The presence and cellular localisation of MMP-13 was assessed using a semiquantitative scoring system. Gelatin zymography was used to detect and measure MMP-13 activity. The zymography was performed on a subset of the cases studied by immunohistochemistry using two groups of 10 paired Dukes's C turnouts and normal samples, selected by either having "good" or "poor" survival.Results: Immunoreactivity to MMP-13 was identified in 91% of cases and immunoreactivity was localised to the cytoplasm of tumour cells. A high MMP-13 staining score showed a trend towards poorer survival. Tumours had significantly greater MMP-13 activity compared with normal colonic mucosa (p < 0.001). Furthermore, the turnout to normal tissue ratio was significantly higher in the poor survival group (p = 0.02).Conclusions: These results show that MMP-13 is frequently present and active in colorectal cancer and suggest that the activity of MMP-13 is associated with poorer survival in colorectal cancer.