Expression of matrix metalloproteinases MMP-2 and MMP-9 in gastric cancer and their relation to claudin-4 expression

Expression of matrix metalloproteinases MMP-2 and MMP-9 in gastric cancer and their relation to claudin-4 expression
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DOI:
10.14670/hh-23.515
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发表时间:
2008-05-01
影响因子:
2
通讯作者:
Hwang, Tsann-Long
Hwang, Tsann-Long
中科院分区:
生物学4区
文献类型:
--
作者:
Lee, Li-Yu;Wu, Chi-Ming;Hwang, Tsann-Long

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基质金属蛋白酶(MMP)MMP-2和MMP-9可以降解细胞外基质和基底膜的IV型胶原。 Claudin-4 是跨膜蛋白 Claudin 大家族的成员,对于紧密连接的形成和维持至关重要。 Claudin-4 已被证明可以激活 MMP-2,这表明 Claudin 介导的癌细胞侵袭增加可能是通过 MMP 蛋白的激活来介导的。为了探讨MMP-2、MMP-9和claudin-4在胃癌中的作用,我们选择了88例胃癌,然后使用免疫组织化学分析这些蛋白的表达。我们发现肠型胃癌中MMP-2、MMP-9和claudin-4的表达均显着高于弥漫型胃癌。进一步分析检测MMP-2、MMP-9表达与claudin-4表达的关系,claudin-4表达与MMP-9表达显着相关,但与MMP-2表达无关。结果表明,MMP-2、MMP-9和claudin-4的表达可能是区分肠型和弥漫型胃癌的表型特征。 claudin-4可能在决定MMP-9活性方面发挥了作用,而MMP-9活性有利于肠型胃癌的远端转移。
Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. Claudin-4 has been shown to activate MMP-2, indicating that claudin-mediated increased cancer cell invasion might be mediated through the activation of MMP proteins. To explore the roles of MMP-2, MMP-9 and claudin-4 in gastric cancer, we selected 88 cases and then analyzed the expression of these proteins using immunohistochemistry. We found that all of MMP-2, MMP-9 and claudin-4 expressions were significantly higher in intestinal-type than in diffuse-type gastric cancer. On further analysis, testing the relationship between MMP-2 and MMP-9 expression with claudin-4 expression, claudin-4 expression was significantly associated with MMP-9 expression, but not with MMP-2 expression. The results showed that MMP-2, MMP-9 and claudin-4 expression may be phenotypic features, distinguishing intestinal-type and diffuse-type gastric cancer. Possibly, claudin-4 played a role in determining MMP-9 activity which favored intestinaltype gastric cancer to distal metastasis.