Relationship of aquaporin 1, 3, and 5 expression in lung cancer cells to cellular differentiation, invasive growth, and metastasis potential
Relationship of aquaporin 1, 3, and 5 expression in lung cancer cells to cellular differentiation, invasive growth, and metastasis potential
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DOI：
10.1016/j.humpath.2010.07.022
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发表时间：
2011-05-01
期刊：
影响因子：
3.3
通讯作者：
Sakuma, Tsutomu
中科院分区：
文献类型：
--
作者：
Machida, Yuichiro;Ueda, Yoshimichi;Sakuma, Tsutomu
水通道蛋白（水的跨膜通道）的致癌能力最近被提出。本研究旨在阐明水通道蛋白1、3和5在肺癌发生发展中的作用。采用免疫组化、Western blot和激光捕获显微切割/实时逆转录聚合酶链反应检测160例不同组织学亚型肺癌组织中水通道蛋白I、3和5的表达，并分析其与临床病理因素和生存期的相关性。水通道蛋白1、3和5分别在71%、40%和56%的肺癌细胞中表达。水通道蛋白在腺癌中表达频繁，而水通道蛋白1和5在鳞状细胞癌中为阴性。非粘液型细支气管肺泡癌细胞的水通道蛋白I和水通道蛋白3位于顶侧或底侧，粘液型细支气管肺泡癌细胞的水通道蛋白I和5及水通道蛋白3位于顶侧或底侧，与非肿瘤性肺组织的水通道蛋白表达一致。非粘液性细支气管肺泡癌的肿瘤发生过程中获得了基底外侧水通道蛋白5的表达。相反，侵袭性腺癌肿瘤细胞过表达水通道蛋白1和5，亚细胞极化丧失，胞浆内分布。水通道蛋白I的过度表达与高术后腺癌转移率和不利的无病生存率相关（P = 0.031）。我们的结论是，水通道蛋白1，3和5在肺癌细胞的表达模式主要与细胞分化。然而，水通道蛋白1和5的表达在侵袭性肺癌细胞中上调，特别是在腺癌中;并且水通道蛋白I的过度表达伴随亚细胞极化的丧失被认为参与了它们的侵袭和转移潜力。(C)2011 Elsevier Inc. All rights reserved.
An oncogenic capacity of aquaporins, transmembrane channels for water, was recently proposed. This study seeks to elucidate the involvement of aquaporin 1, 3, and 5 in the development and progression of lung cancer. Expression of aquaporin I, 3, and 5 was examined by immunohistochemistry, Western blot, and laser-captured microdissection/real-time reverse transcription polymerase chain reaction in 160 lung cancers of various histologic subtypes; and its correlation with clinicopathological factors and survival was analyzed. Aquaporin 1, 3, and 5 were expressed in tumor cells in 71%, 40%, and 56% of lung cancers, respectively. Aquaporin expressions were frequent in adenocarcinomas, whereas aquaporin 1 and 5 were negative in squamous cell carcinomas. Bronchioloalveolar carcinoma cells exhibited an apicolateral aquaporin I and apicolateral or basolateral aquaporin 3 localization in nonmucinous type, and apical aquaporin I and 5 and basolateral aquaporin 3 expression in mucinous type, which corresponded to aquaporins expression of nonneoplastic lung tissue. Basolateral aquaporin 5 expression was acquired during tumorigenesis of nonmucinous bronchioloalveolar carcinoma. In contrast, invasive adenocarcinoma tumor cells overexpressed aquaporin 1 and 5 with loss of subcellular polarization and with an intracytoplasmic distribution. Overexpression of aquaporin I correlated with high postoperative adenocarcinoma metastasis ratios and unfavorable disease-free survival rates (P = .031). We conclude that expression patterns of aquaporin 1, 3, and 5 in lung cancer cells are mostly associated with cellular differentiation. However, the expression of aquaporin 1 and 5 is up-regulated in invading lung cancer cells, particularly in adenocarcinomas; and the overexpression of aquaporin I with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential. (C) 2011 Elsevier Inc. All rights reserved.