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 1, 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 1 and apicolateral or basolateral
aquaporin 3 localization in nonmucinous type, and apical
aquaporin 1 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 1 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 1 with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential.