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Relationship between expression of matrix metalloproteinase-7 and clinic-opathobiological behaviors of gastric cancer
Ji-Min Sun, Hua-Chuan Zheng, Xue-Fei Yang, Yan Xin, Yin-Chang Zhang
Ji-Min Sun, Hua-Chuan Zheng, Xue-fei Yang, Yan Xin, Yin-Chang Zhang, Cancer Institute, The First Affiliated Hospital of China Medical University, Nanjing North Street 155, Shenyang 110001, Liaoning Province, China
Correspondence to: Ji-Min Sun, Cancer Institute, The First Affiliated Hospital of China Medical University, Nanjing North Street 155, Shenyang 110001, Liaoning Province, China. sun-jinmin@hotmail.com
Received: November 19, 2002 Revised: November 23, 2002 Accepted: November 28, 2002 Published online: September 15, 2003
AIM
To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesis and progression of gastric cancer.
METHODS
We studied MMP-7 expression and microvessel density (MVD) in primary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method with anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD in primary foci were compared with clinicopathological features of tumors, and the relationship between MMP-7 expression and mean microvessel densities (MVD) in gastric cancer was concerned as well.
RESULTS
MMP-7 showed positive expression in 29.2 % (33/113) of adjacent mucosa of gastric cancer was less than that in its primary foci (69.0 %, 78/113) of gastric cancer. MMP-7 expression in primary foci was closely correlated with tumor size, invasive depth, metastasis and TNM staging of gastric cancer (P <0.05) despite no significant relationship between its expression and differentiation or growth pattern (P >0.05). Positive correlation of mean MVD with tumor size, depth of invasion, metastasis and TNM staging was found (P <0.05), but no relationship was found between mean MVD or differentiation of gastric cancer (P >0.05). Especially, mean MVD was dependent on MMP-7 expression in gastric cancer (P <0.05).
CONCLUSION
MMP-7 is an effective marker to reveal the biological behaviors of gastric cancer and plays an important role in carcinogenesis and progression of gastric cancer by participating in growth, invasion, metastasis and angio-genesis.
Key Words: N/A
Citation: Sun JM, Zheng HC, Yang XF, Xin Y, Zhang YC. Relationship between expression of matrix metalloproteinase-7 and clinic-opathobiological behaviors of gastric cancer. Shijie Huaren Xiaohua Zazhi 2003; 11(9): 1310-1313
本组资料中MMP-7在29.3 %的胃癌旁黏膜中呈阳性表达, 但仍然不可忽视, 因为本组病例中的癌旁黏膜大多伴有肠化生和炎症等病理学变化. 有文献报道IL-2, IL-8等炎症因子可使上皮细胞中MMP-7表达上调[26]. Crawford et al [26]研究发现MMP-7和FasL在胰腺化生导管上皮细胞中协同表达, 提示MMP-7参与胰腺导管化生细胞FasL水解, 进而调节导管上皮细胞的凋亡和增生平衡. Yu et al [27]研究结果显示MMP-7可以和CD44、EGF结合而参与上皮细胞的修复过程. 这些研究均提示MMP-7在胃黏膜的修复和再生等生理过程中起重要调节作用.
为了观察MMP-7在胃癌组织中的表达, 我们比较了MMP-7在胃癌旁黏膜和癌组织中的阳性表达率, 结果发现胃癌中MMP-7中表达高于癌旁黏膜, 提示MMP-7表达上调参与胃癌发生过程. 此外, 本研究显示即使分化型胃癌中MMP-7表达低于与未分化胃癌, 但MMP-7表达与胃癌的分化程度无显著相关性, 说明MMP-7表达上调是胃癌的普遍现象, 不能反映胃癌的分化程度. 我们也发现MMP-7阳性表达与胃癌肿块大小、浸润深度、转移和TNM分期密切相关, 由此可推测MMP-7可能参与胃癌的生长、浸润和转移等过程. Giatromanolaki et al [28]研究发现MMP-7可以水解介导细胞同质性黏附的关键分子E-cadherin, 进而提高肿瘤细胞运动性和浸润能力, 使肿瘤细胞更具恶性表型. Adachi et al [25]将MMP-7 cDNA转染到结肠癌细胞后其浸润和转移能力大大提高. 同时有文献报道MMP-7水解其他金属蛋白酶的活化和参与FasL、肿瘤坏死因子释放[5,6]. 因此MMP-7可能通过水解细胞外基质、参与免疫逃逸和提高细胞运动能力等方面参与胃癌细胞的演进过程.
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