Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma
Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma
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DOI：
10.1111/j.1349-7006.2007.00488.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Mukai, Kiyoshi
中科院分区：
文献类型：
--
作者：
Iwaya, Keiichi;Oikawa, Kosuke;Mukai, Kiyoshi
当肌动蛋白相关蛋白2和3复合体(Arp2/3复合体)触发肌动蛋白聚合，与WAVE2结合后立即形成片状脂膜时，正常细胞就会发生定向运动。为了探讨这种机制是否与结直肠癌肝转移有关，采用免疫组织化学方法检测了154例结直肠癌肝转移标本(29例有肝转移和125例无肝转移)中Arp2和WAVE2的表达。在同一癌细胞中有55例(35.7%)同时表达Arp2和WAVE2，而在正常结肠上皮细胞中未见表达。单变量分析显示，共定位显著预测肝转移(风险比[RR]8.760。同样，组织学分级(RR2.46)、淋巴侵犯(RR9.95)和肿瘤萌发(RR4.00)也是显著的预测因素。多因素分析显示，共局灶和淋巴侵犯是独立的危险因素。用实时定量聚合酶链式反应检测59例大肠组织中Arp2基因的表达。原位杂交显示，癌细胞表达的Arp2的高mRNA水平与肝转移显著相关。然而，其作用被与Arp2高表达密切相关的共定位风险的影响所吸收。这些结果表明，Arp2和WAVE2的共存是结直肠癌肝转移的独立危险因素。
Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma.