Abstract
An oncogenic capacity of aquaporins (AQPs), transmembrane channels for water, was recently proposed. This study seeks to elucidate the involvement of AQP1, 3 and 5 in the development and progression of lung cancer. Expression analyses of AQP1, 3 and 5 by immunohistochemistry, western blot and real time RT-PCR in 160 lung cancers showed that AQP1, 3 and 5 were expressed in tumor cells of 71, 40 and 56%, of lung cancers, respectively. AQPs expressions were frequent in adenocarcinomas (ADCs), while AQP1 and 5 were negative in squamous cell carcinomas. Bronchioloalveolar carcinoma (BAC) cells exhibited an apicolateral AQP1 and apicolateral or basolateral AQP3 localization in non-mucinous type, and apical AQP1 and 5 and basolateral AQP3 expression in mucinous type, which corresponded to AQPs expression of non-neoplastic lung tissue. Basolateral AQP5 expression was acquired during tumorigenesis of non-mucinous BAC. In contrast, invasive ADC tumor cells, either with fibroblastic reaction or papillary growth in the alveolar space, overexpressed AQP1 and 5 with loss of subcellular polarization and with an intracytoplasmic distribution. Overexpression of AQP1 correlated with high postoperative ADC metastasis ratios and unfavorable disease-free survival rates (p=0.031). We conclude that expression patterns of AQP1, 3 and 5 in lung cancer cells are mostly associated with cellular differentiation. However, the expression of AQP1 and 5 is up-regulated in invading lung cancer cells, particularly in ADCs, and the overexpression of AQP1 with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential.
- © 2011 ERS
