Xu Xianhua, Kim Ji Eun, Sun Ping-Li, Yoo Seol Bong, Kim Hyojin, Jin Yan, Chung Jin-Haeng
Department of Pathology, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China.
Department of Pathology, Seoul National University Boramae Hospital, Seoul 156-707, Republic of Korea.
Exp Ther Med. 2015 Feb;9(2):311-318. doi: 10.3892/etm.2014.2095. Epub 2014 Nov 28.
The protein β-catenin exhibits a dual function in cells, by acting as a major structural component of cell-cell adherens junctions and as a central signaling molecule in the Wnt signaling pathway. However, how the regulation of β-catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC) varies according to histological type remains unclear. To investigate the regulatory mechanism of β-catenin on tumor metastasis, the present study compared the expression of Wnt1, β-catenin and E-cadherin in 41 primary NSCLC tumors and their corresponding metastatic lesions by immunohistochemistry. Altered expression of β-catenin was more frequent in the metastatic tumors (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05). There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell carcinoma (SqCC)] that revealed discordant β-catenin expression between the primary tumors and the corresponding metastatic lesions. Of these, 11 cases (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired β-catenin alterations in the metastatic lesions. Subgroup analysis of these nine ADCs revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant β-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired β-catenin expression during metastatic progression with Wnt1 overexpression but no change in E-cadherin expression. One case of SqCC revealed normal β-catenin expression in the metastasis although the expression was aberrant in the primary tumor. The results of the present study revealed that the changes in β-catenin expression occurred during tumor metastasis by different mechanisms, depending on histological type. The alterations in β-catenin expression may be regulated by a cadherin-catenin system in ADCs with reduced membranous expression of E-cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or nuclear transition types.
蛋白质β-连环蛋白在细胞中具有双重功能，它既是细胞间黏附连接的主要结构成分，也是Wnt信号通路中的核心信号分子。然而，在非小细胞肺癌（NSCLC）肿瘤转移过程中，β-连环蛋白表达的调控如何因组织学类型而异仍不清楚。为了研究β-连环蛋白对肿瘤转移的调控机制，本研究通过免疫组织化学比较了41例原发性NSCLC肿瘤及其相应转移灶中Wnt1、β-连环蛋白和E-钙黏蛋白的表达。β-连环蛋白表达改变在转移瘤中（34/41，82.9%）比在相应的原发性肿瘤中（24/41，58.5%；P<0.05）更常见。有12例[9例腺癌（ADC）和3例鳞状细胞癌（SqCC）]在原发性肿瘤和相应转移灶之间显示出β-连环蛋白表达不一致。其中，11例（11/12，91.7%；9例ADC和2例SqCC）在转移灶中表现出获得性β-连环蛋白改变。对这9例ADC的亚组分析显示，6例（6/9，66.7%）伴有E-钙黏蛋白缺失但无Wnt1过表达。对3例SqCC的亚组分析显示β-连环蛋白表达不一致。2例（2/3，66.7%）在转移进展过程中表现出获得性β-连环蛋白表达且伴有Wnt1过表达，但E-钙黏蛋白表达无变化。1例SqCC在转移灶中显示β-连环蛋白表达正常，尽管在原发性肿瘤中表达异常。本研究结果表明，β-连环蛋白表达的变化在肿瘤转移过程中通过不同机制发生，这取决于组织学类型。β-连环蛋白表达的改变可能在E-钙黏蛋白膜表达降低的ADC中由钙黏蛋白-连环蛋白系统调节，但在具有细胞质或核转位类型的SqCC中由Wnt1过表达介导。
