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Vol.52 No.1 contents | Japanese/English |
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- Original Article -
The Aquaporin Family: A Novel Player in the Progression of Adenocarcinoma of the Lung
Yuichiro Machida1, Yoshimichi Ueda2, Masakatsu Ueno1, Ryo Tanaka1, Kouichi Aikawa1, Katsuo Usuda1, Motoyasu Sagawa1, Tsutomu Sakuma11Department of Thoracic Surgery, 2Department of Pathology, Kanazawa Medical University, Japan
Objective. Aquaporins (AQPs) are a family of small (-28 kDa/monomer) channel-forming membrane proteins that function as osmotically driven transepithelial and transcellular water transporters. To date, 13 homologous members have been identified in mammals. Recent studies using several varieties of aquaporin-gene knock-out mice have indicated previously unanticipated roles for AQPs, including cell cycle control and migration. In this review, we summarize the recent data on the involvement of AQPs in the progression of adenocarcinoma of the lung. Results. AQP1, 3, 4 and 5 were demonstrated in normal lung tissue with cell type-specific and polarized patterns. AQP1, 3 and 5 were frequently expressed in lung adenocarcinoma tissue subtypes. There were 3 recognized AQP-expression patterns: 1) a polarized expression of AQP1 and 3 in accordance with the differentiation of normal lung cells; 2) a polarized but aberrant expression of AQP5, and 3) the overexpression in the absence of any polarity of AQP1 and 5. Pattern 1) was seen predominantly in bronchioloalveolar carcinoma cells, of either non-mucinous or mucinous type, and decreased according to the progression of the disease. Pattern 2) was detected not only in bronchioloalveolar carcinoma cells, but also in atypical adenomatous hyperplasia cells, which suggested a relationship between AQP5 expression and the tumorigenesis of adenocarcinoma. Pattern 3) has been increasingly observed in the areas with micro-invasion, becoming prominent in the areas with widespread invasion, and correlated significantly with the decreased survival rates observed in adenocarcinoma patients. The oncogenic roles of each pattern were determined by in vitro studies using tumor cells with the AQP cells either knocked-in or knocked-out. Overexpressed AQP1 facilitated lamellipodia formation at the front line of the invasion, and AQP5 activated intracytoplasmic signal molecules, which play critical roles in cellular proliferation and epithelial mesenchymal transition (EMT). The involvement of AQP5 in the secretion of mucin in mucinous tumors and AQP1 in the aggressiveness of micropapillary components were also observed. The level of AQP4 expression was high in lung adenocarcinoma, and correlated significantly with a more favourable prognosis in adenocarcinoma patients. Conclusion. Several studies indicate that AQP1 and 5 are vital activators of the EMT of lung adenocarcinoma, suggesting that AQP can be a novel target molecule for counteracting the aggressiveness of lung adenocarcinoma.
key words: Lung adenocarcinoma, Aquaporin
Received: June 1, 2011
Accepted: January 13, 2012
JJLC 52 (1): 17-22, 2012
