Abstract
Aquaporin 5 (AQP5) promotes the progression and invasion of several cancers, but its role in the tumorigenesis of human gastric carcinoma (GC) has not been clearly defined. Here, we investigated the potential functions of AQP5 in the proliferation and migration of human GC. RT-PCR and western blotting were used to detect the expression of AQP5 in human GC cell lines. Immunohistochemistry was applied to evaluate the expression of AQP5 in human GC tissues and corresponding normal tissues. Following ectopic overexpression of AQP5 or inhibition of AQP5 by its inhibitor, acetazolamide (AZA), cell proliferation and migration of AGS cells were analyzed by MTT assay, colony formation assay, and wound healing assay. Heterogeneous expression of AQP5 mRNA and protein was observed in human GC cell lines MKN45, MKN28, AGS, and SGC7901. AQP5 was up-regulated in GC tissues in comparison to corresponding normal tissues. AQP5 protein was mainly localized in the cell membrane. Overexpression of AQP5 was correlated with enhanced lymph node metastasis. In vitro, overexpression of AQP5 notably enhanced, while inhibition of AQP5 by AZA significantly attenuated the proliferation and migration of AGS cells. Our data indicate that AQP5 may play an important role in the tumorigenesis and progression of human GC and suggest that AQP5 is a potential therapeutic target against GC.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.
Nielsen S, Frokiaer J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002;82:205–44.
Papadopoulos MC, Saadoun S, Verkman AS. Aquaporins and cell migration. Pflügers Arch. 2007;456:693–700.
Hu J, Verkman AS. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. FASEB J. 2006;20:1892–4.
Cao C, Sun Y, Healey S, et al. EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. Biochem J. 2006;400:225–34.
Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature. 2005;434:786–92.
Saadoun S, Papadopoulos MC, Watanabe H, et al. Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci. 2005;118:5691–98.
Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol. 2008;28:326–32.
Raina S, Preston GM, Guggino WB, Agre P. Molecular cloning and characterization of an aquaporin cDNA from salivary, lacrimal, and respiratory tissues. J Biol Chem. 1995;270:1908–12.
Parvin MN, Tsumura K, Akamatu T, Kanamori N, Hosoi K. Expression and localization of AQP5 in the stomach and duodenum of the rat. Biochim Biophys Acta. 2002;1542:116–24.
Kang SK, Chae YK, Woo J, et al. Role of human Aquaporin 5 in colorectal carcinogenesis. Am J Pathol. 2008;173:518–25.
Najbauer J, Kim M-J, Woo J, et al. Expression of Aquaporin 5 (AQP5) Promotes tumor invasion in human non small cell lung cancer. PLoS One. 2008;3:e2162.
Blagosklonny MV, Chae YK, Kang SK, et al. Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PLoS One. 2008;3:e2594.
Jung HJ, Park J-Y, Jeon H-S, Kwon T-H. Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells. PLoS One. 2011;6:e28492.
Sekine S, Shimada Y, Nagata T, et al. Prognostic significance of aquaporins in human biliary tract carcinoma. Oncol Rep. 2012;27:1741–47.
Zhang Z, Chen Z, Song Y, et al. Expression of aquaporin 5 increases proliferation and metastasis potential of lung cancer. J Pathol. 2010;221:210–20.
Watanabe T, Fujii T, Oya T, et al. Involvement of aquaporin-5 in differentiation of human gastric cancer cells. J Physiol Sci. 2009;59:113–22.
Shen L, Zhu Z, Huang Y, et al. Expression profile of multiple aquaporins in human gastric carcinoma and its clinical significance. Biomed Pharmacother. 2010;64:313–8.
Ameli PA, Madan M, Chigurupati S, et al. Effect of acetazolamide on aquaporin-1 and fluid flow in cultured choroid plexus. Acta Neurochir Suppl. 2012;113:59–64.
Tanimura Y, Hiroaki Y, Fujiyoshi Y. Acetazolamide reversibly inhibits water conduction by aquaporin-4. J Struct Biol. 2009;166:16–21.
Ran X, Wang H, Chen Y, et al. Aquaporin-1 expression and angiogenesis in rabbit chronic myocardial ischemia is decreased by acetazolamide. Hear Vessel. 2010;25:237–47.
Zhang Z-Q, Zhu Z-X, Bai C-X. Lung fluorescence imaging to evaluate tumor metastasis induced by AQP5 expression in murine model. Med Oncol. 2010;29:205–11.
Moon C, Soria JC, Jang SJ, et al. Involvement of aquaporins in colorectal carcinogenesis. Oncogene. 2003;22:6699–703.
Sakitani K, Hirata Y, Watabe H, et al. Gastric cancer risk according to the distribution of intestinal metaplasia and neutrophil infiltration. Gastroenterol Hepatol. 2011;26:1570–5.
Chen Z, Zhang Z, Gu Y, Bai C. Impaired migration and cell volume regulation in aquaporin 5-deficient SPC-A1 cells. Respir Physiol Neurobiol. 2011;176:110–7.
Chae YK, Woo J, Kim MJ, et al. Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PLoS One. 2008;3:e2162.
Woo J, Lee J, Kim MS, et al. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun. 2008;367:291–8.
Acknowledgements
We thank Dr. Shi-wen Luo for suggestion. This work was supported by the National Science Foundation of China (no. 81270479) and the Health Foundation of Jiangxi Province (no. 20112011).
Conflict of interest
The authors declare that there is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, YH., Zhou, XY., Wang, HM. et al. Aquaporin 5 promotes the proliferation and migration of human gastric carcinoma cells. Tumor Biol. 34, 1743–1751 (2013). https://doi.org/10.1007/s13277-013-0712-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-013-0712-4