Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer.
Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer.
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DOI：
10.1007/pl00011698
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发表时间：
2000-09-29
期刊：
影响因子：
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通讯作者：
Sasaki, Takuma
中科院分区：
文献类型：
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作者：
Yonemura, Yutaka;Endou, Yoshio;Sasaki, Takuma
背景：基质金属蛋白酶-7（MMP-7）是一种重要的基质降解酶，在癌症的侵袭和转移中发挥重要作用。为探讨胃癌腹膜转移的形成机制，本研究通过检测MMP-7在胃癌原发灶和腹膜转移灶中的mRNA和蛋白表达，探讨MMP-7在胃癌腹膜转移中的作用。应用免疫组化和逆转录-聚合酶链反应（RT-PCR）技术对136例患者的乳腺癌组织进行检测，并与临床病理参数进行比较。MMP-7 mRNA在53例原发性胃癌中有28例（53%）表达，而在正常胃粘膜、成纤维细胞和间皮细胞中无表达。免疫组化结果显示，MMP-7主要分布于癌细胞的胞膜和胞浆。在136例原发性肿瘤中，70例（53%）MMP-7过表达，MMP-7的表达与肿瘤的浸润深度、淋巴结转移、低分化程度及腹膜转移密切相关。与MMP-7阴性肿瘤患者相比，MMP-7阳性肿瘤患者的生存率明显更差，死于腹膜复发的频率更高。6例腹膜播散组织均表达MMP-7 mRNA，14例腹膜播散组织中有13例抗人MMP-7单克隆抗体阳性。Logistic回归分析显示，MMP-7免疫组织学状态是腹膜转移的独立危险因素，MMP-7 mRNA阳性患者腹膜转移的相对危险性高9.9倍。这些结果强烈提示MMP-7可能在胃癌腹膜播散的形成中起重要作用，并且在腹膜内游离癌细胞从腹膜表面侵入腹膜下组织的过程中可能发生具有MMP-7过表达的癌细胞的克隆选择。MMP-7在原发肿瘤中的组织状态可能是腹膜播散的良好指标。
BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading enzyme that has a large role in the invasion and metastasis of cancer. To discover the mechanism of the formation of peritoneal dissemination in gastric cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric cancers and peritoneal dissemination.METHODS: MMP-7 expression in primary gastric cancers (136 patients) was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with chinicopathological parameters.RESULTS: MMP-7 mRNA was expressed in 28 (53%) of 53 primary gastric cancers, but not in normal gastric mucosa, fibroblasts, or mesothelial cells. An immunohistochemical method demonstrated that MMP-7 immunoreactivity was found on the cell membrane and cytoplasm of cancer cells. Among 136 primary tumors, 70 (53%) tumors overexpressed MMP-7, and MMP-7 tissue status had significant positive correlation with serosal involvement, lymph node metastasis, poor differentiation of cancer, and peritoneal dissemination. Patients with MMP-7-positive tumor had significantly poorer survival and more frequently died of peritoneal recurrence than did those with MMP-7-negative tumors. All 6 examined peritoneal disseminations expressed MMP-7 mRNA, and 13 of 14 peritoneal disseminations showed immunoreactivity to anti-human MMP-7 monoclonal antibody. Logistic regression analysis showed that MMP-7 immunohistological status was an independent risk factor for peritoneal dissemination, and patients with MMP-7 mRNA-positive tumors had a 9.9-fold higher relative risk for peritoneal metastasis.CONCLUSION: These results strongly suggest that MMP-7 may have a large role in the formation of peritoneal dissemination in gastric cancer, and that clonal selection of cancer cells with MMP-7 overexpression may occur during the invasion of intraperitoneal free cancer cells from the peritoneal surface into the subperitoneal tissue. MMP-7 tissue status in the primary tumor may be a good indicator of peritoneal dissemination.