Aquaporin 5 has been recently found as an important oncogenic marker whose
expression levels seem to be determined by the level of cellular differentiation.
Despite aquaporin volume decrease (AVD) being the most conserved earliest event
in apoptosis, there is still a paucity of studies exploring on aquaporin expression
and its relationship with apoptosis in cancer. The aim of this study was to investigate
the expression of aquaporin 5 channel protein and to explore on its relationship
with apoptosis in well and poorly differentiated non-small cell lung carcinoma both in-vivo and in-vitro. Findings from the study showed that the expression of AQP5
both in-vivo and in-vitro was dependent on the type and degree of tumour differentiation. In-vivo, an increase in aquaporin 5 expression
was associated with an increased apoptosis in both poorly and highly differentiated
adenocarcinoma (AC) while there was no association between aquaporin 5 expression
and apoptosis in both poorly and highly differentiated squamous cell carcinoma (SCC). In vitro, differentiation therapy in the
form of ATRA decreased both cell proliferation and increased the expression of AQP5
in A549 cells. The cytomorphological changes, expression of differentiation markers
and flow cytometry apoptotic results were dependent on the dose of ATRA treatment.
In conclusion, a higher expression of aquaporin 5 was found to promote the rate
of the apoptotic process in lung adenocarcinoma (AC).
References
[1]
Walz, T., Fujiyoshi, Y. and Engel, A. (2009) The Aquaporin Structure and Functional Implications. Handbook of Experimental Pharmacology, 190, 31-56.
[2]
Kong, H., Sha, L., Fan, Y., Xiao, M., Ding, J., Wu, J. and Hu, G. (2009) Requirement of AQP4 for Antidepressive Efficiency of Fluoxetine: Implication in Adult Hippocampal Neurogenesis. Neuropschopharmacology, 34, 1263-1276.
http://dx.doi.org/10.1038/npp.2008.185
[3]
Zheng, G., Li, Y., Gu, Y., Chen, X., Zhou, Y., Zhao, S. and Shen, J. (2010) Beyond Water Channel: Aquaporin 4 in Adult Neurogenesis. Neurochemistry International, 56, 651-654. http://dx.doi.org/10.1016/j.neuint.2010.01.014
[4]
Saadoun, S., Papadopoulos, M.C., Davies, D.C., Krishna, S. and Bell, B.A. (2002) Aquaporin 4 Expression Is Increased in Odematous Human Brain Tumours. Journal of Neurology, Neurosurgery & Psychiatry, 72, 262-265.
http://dx.doi.org/10.1136/jnnp.72.2.262
[5]
Warth, A., Simon, P., Capper, D., Goeppert, B., Tabatabai, G., Herzog, H., Dietz, K., Stubenvoll, F., Ajaaj, R., Becker, R., Weller, M., Meyermann, R., Wolburg, H. and Mittelbronn, M. (2007) Expression Pattern of the Water Channel Aquaporin-4 in Human Gliomas Is Associated with Blood-Brain Barrier Disturbance But Not with Patient Survival. Journal of Neuroscience Research, 85, 1336-1345. http://dx.doi.org/10.1002/jnr.21224
[6]
Otterbach, F., Calliers, R., Kimmig, R., Schmid, K.W. and Bankfalvi, A. (2008) Aquaporin-1 Expression in Invasive Breast Carcinoma. Der Pathologe, 29, 357-362. http://dx.doi.org/10.1007/s00292-008-1039-6
[7]
Kang, S.K., Chae, Y.K., Woo, J., Kim, S.K., Park, J.C., Lee, J., Soria, J.C., Jang, J.S., Sidransky, D. and Moon, C. (2008) Role of Human Aquaporin 5 in Colorectal Carcinogenesis. The American Journal of Pathology, 173, 518-525.
http://dx.doi.org/10.2353/ajpath.2008.071198
[8]
Nico, B. and Ribatti, D. (2010) Aquaporins in Tumor Growth and Angiogenesis. Cancer Letters, 28, 135-138.
http://dx.doi.org/10.1016/j.canlet.2010.02.005
[9]
Moon, C., Soria, J.C., Jang, S.J., Lee, J., Hoque, M.O., Sibony, M., Trink, B., Chang, Y.S., Sidransky, D. and Mao, L. (2003) Involvement of Aquaporins in Colorectal Carcinogenesis. Oncogene, 22, 6699-6703.
http://dx.doi.org/10.1038/sj.onc.1206762
[10]
Yang, J.H., Shi, Y.F., Cheng, Q. and Deng, L. (2006) Expression and Localization of Aquaporin 5 in the Epithelial Ovarian Tumours. Gynecologic Oncology, 100, 294-299. http://dx.doi.org/10.1016/j.ygyno.2005.08.054
[11]
Woo, J., Lee, J. and Chae, Y.K. (2008) Overexpression of AQP5, a Putative Oncogene, Promotes Cell Growth and Transformation. Cancer Letters, 264, 54-62. http://dx.doi.org/10.1016/j.canlet.2008.01.029
[12]
Huang, Y.H., Zhou, X.Y., Wang, H.M., Xu, H., Chen, J. and Lu, N.H. (2013) Aquaporin 5 Promotes the Proliferation and Migration of Human Gastric Carcinoma Cells. Tumour Biology, 34, 1743-1751.
http://dx.doi.org/10.1007/s13277-013-0712-4
[13]
Yi, F., Khan, M., Gao, H., Hao, F., Sun, M., Zhong, L., Lu, C., Feng, X. and Ma, T. (2012) Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin 5 Deficiency. Stem Cells and Development, 21, 2495-2507. http://dx.doi.org/10.1089/scd.2011.0597
[14]
Machida, Y., Ueda, Y., Shimasaki, M., Sato, K., Sagawa, M., Katsuda, S. and Sakuma, T. (2010) Relationship of Aquaporin 1, 3, and 5 Expression in Lung Cancer Cells to Cellular Differentiation, Invasive Growth and Metastatis Potential. Human Pathology, 42, 669-678. http://dx.doi.org/10.1016/j.humpath.2010.07.022
[15]
Kerr, J.F.R., Wyllie, A.H. and Currie, A.R. (1972) Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics. British Journal of Cancer, 26, 239-257. http://dx.doi.org/10.1038/bjc.1972.33
[16]
Mattern, J. and Volm, M. (2004) Imbalance of Cell Proliferation and Apoptosis during Progression of Lung Carcinomas. Anticancer Research, 24, 4243-4246.
[17]
Hughes Jr., F.M., Bortner, C.D., Purdy, G.P. and Cidlowski, J.A. (1997) Intracellular K+ Suppresses the Activation of Apoptosis in Lymphocytes. The Journal of Biological Chemistry, 272, 30567-30576.
http://dx.doi.org/10.1074/jbc.272.48.30567
[18]
Perez, G.I., Maravei, D.V., Trbovich, A.M., Cidlowski, J.A., Tilly, J.L. and Hughes Jr., F.M. (2000) Identification of Potassium-Dependent and -Independent Components of the Apoptotic Machinery in Ovarian Germ Cells and Granulosa Cells. Biology of Reproduction, 63, 1358-1369. http://dx.doi.org/10.1095/biolreprod63.5.1358
[19]
Jablonski, E.M., Mattocks, M.A., Sokolov, E., Koniaris, L.G., Hughes, F.M., Fausto, N., Pierce, R. and McKillop, I. (2007) Decreased Aquaporin Expression Leads to Increased Resistance to Apoptosis in Hepatocellular Carcinoma. Cancer Letters, 250, 36-46. http://dx.doi.org/10.1016/j.canlet.2006.09.013
[20]
Orlov, S.N., Model, M.A. and Grygorczyk, R. (2013) CrossTalk Opposing View: The Triggering and Progression of the Cell Death Machinery Can Occur without Cell Volume Perturbations. The Journal of Physiology, 591, 6123-6125.
http://dx.doi.org/10.1113/jphysiol.2013.258624
[21]
Chae, Y.K., Sung, K.K., Myoung, S.K., Janghee, W., Juna, L., Steven, C., Dong-Wook, K., Myungshin, K., Seonyang, P., Inho, K., Bhumsuk, K., Jiyoung, R., Nam, H.K., Gyeongsin, P., Soo-Hyun, K., Se-Eun, J., Il-Young, K., David, S. and Chulso, M. (2008) Human AQP5 Plays a Role in the Progression of Chronic Myelogenous Leukemia (CML). PLoS ONE, 3, e2594. http://dx.doi.org/10.1371/journal.pone.0002594
[22]
Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., Jemal, D.V.M., Yu, X.Q. and He, J. (2015) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. http://dx.doi.org/10.3322/caac.21338
[23]
Tormanen, U., Eerola, A.K., Rainio, P., Vahakangas, K., Soini, Y., Sormunen, E., Bloigu, R., Lehto, V.-P. and Paakko, P. (1995) Enhanced Apoptosis Predicts Shortened Survival in Non-Small Cell Lung Carcinoma. Cancer Research, 55, 5595-5602.
[24]
Tanaka, F., Kawano, Y., Li, M., Takata, T., Miyahara, R., Yanagihara, K., Ohtake, Y., Fukuse, T. and Wada, H. (1999) Prognostic Significance of Apoptotic Index in Completely Resected Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 17, 2728-2736.
[25]
Potten, C.S. (1996) What Is an Apoptotic Index Measuring? A Commentary. British Journal of Cancer, 74, 1743-1748.
http://dx.doi.org/10.1038/bjc.1996.624
[26]
Zou, C.P., Kurie, J.M., Lotan, D., Zou, C.C., Hong, W.K. and Lotan, R. (1998) Higher Potency of N-(4-Hydroxyphenyl)retinamide than All-Trans-Retinoic Acid in Induction of Apoptosis in Non-Small Cell Lung Cancer Cell Lines. Clinical Cancer Research, 4, 1345-1355.
[27]
Hansen, L.A., Sigma, C.C., Andreola, F., Ross, S.A., Kelloff, G.S. and De Luca, L.M. (2000) Retinoids in Chemoprevention and Differentiation Therapy. Carcinogenesis, 21, 1271-1279. http://dx.doi.org/10.1093/carcin/21.7.1271
[28]
Choi, E.J., Whang, Y.I., Kim, S.K., Kim, J.H. and Kim, Y.H. (2007) Combinational Treatment with Retinoic Acid Derivatives in Non-Small Cell Lung Carcinoma in Vitro. Journal of Korean Medical Science, 22, S52-S60.
http://dx.doi.org/10.3346/jkms.2007.22.S.S52
[29]
Roy, R., Willan, P.M., Clarke, R. and Farnie, G. (2010) Differentiation Therapy: Targeting Breast Cancer Stem Cells to Reduce Resistance to Radiotherapy and Chemotherapy. Breast Cancer Research, 12, O5.
http://dx.doi.org/10.1186/bcr2496
[30]
So, P.L., Fujimoto, M.A. and Epstein Jr., E.H. (2008) Pharmacologic Retinoid Signaling and Physiologic Retinoic Acid Receptor Signaling Inhibit Basal Cell Carcinoma Tumorigenesis. Molecular Cancer Therapeutics, 7, 1275-1284.
http://dx.doi.org/10.1158/1535-7163.MCT-07-2043
[31]
Chang, Q., Chen, Z., You, J., McNutt, M.A., Zhang, T., Han, Z., Zhang, X., Gong, E. and Gu, J. (2007) All-Trans-Retinoic Acid Induces Cell Growth Arrest in a Human Medulloblastoma Cell Line. Journal of Neuro-Oncology, 84, 263-267. http://dx.doi.org/10.1007/s11060-007-9380-9
[32]
Zhang, Z., Chen, Z., Song, Y., Zhang, P., Hu, J. and Bai, C. (2010) Expression of Aquaporin 5 Increases Proliferation and Metastasis Potential of Lung Cancer. Journal of Pathology, 221, 210-220. http://dx.doi.org/10.1002/path.2702
[33]
Singer, B.B., Scheffrahn, I., Kammerer, R., Suttorp, N., Ergun, S. and Slevogt, H. (2010) Deregulation of the CEACAM Expression Pattern Causes Undifferentiated Cell Growth in Human Lung Adenocarcinoma Cells. PLoS ONE, 5, e8747. http://dx.doi.org/10.1371/journal.pone.0008747
[34]
Jung, H.J., Park, J.-Y., Jeon, H.-S. and Kwon, T.-H. (2011) Aquaporin-5: A Marker Protein for Proliferation and Migration of Human Breast Cancer Cells. PLoS ONE, 6, e28492. http://dx.doi.org/10.1371/journal.pone.0028492
[35]
Jablonski, E.M., Webb, A.N., McConnell, N.A., Riley, M.C. and Hughes Jr., F.M. (2004) Plasma Membrane Aquaporin Activity Can Affect the Rate of Apoptosis but Is Inhibited after Apoptotic Volume Decrease. American Journal of Physiology—Cell Physiology, 286, C975-C985. http://dx.doi.org/10.1152/ajpcell.00180.2003
