|Year : 2017 | Volume
| Issue : 1 | Page : 137-138
Role of aquaporins in oral cancer
Mamatha G. S. Reddy, Elizabeth Dony
Department of Oral Pathology and Microbiology, Dr. D. Y. Patil University's, Dr. D. Y. Patil Dental College and Hospital, Pune, Maharashtra, India
|Date of Web Publication||21-Apr-2017|
Mamatha G. S. Reddy
Department of Oral Pathology and Microbiology, Dr. D. Y. Patil University's, Dr. D. Y. Patil Dental College and Hospital, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Aquaporins (AQP) are the membrane proteins involved in the transport of water and some neutral solutes. Thirteen types of AQP are identified in various human tissues. The expression of AQP's has been studied in various tumors among one is oral cancer. These molecules are involved in cell proliferation, migration, and metastasis. AQP target inhibitors act directly or indirectly through focal adhesion kinase-mitogen-activated protein kinase signaling pathway and shown promising results along with anti-cancer drugs. However, further researches were required to verify the efficiency and safety of these AQPs-target inhibitors in clinical therapy.
Keywords: Aquaporin, aquaporin 1, oral cancer
|How to cite this article:|
Reddy MG, Dony E. Role of aquaporins in oral cancer. J Can Res Ther 2017;13:137-8
| > Introduction|| |
Aquaporins (AQP) are a family of integral transmembrane proteins that serve as channels in the selective transfer of water, and in some cases, small solutes across the membrane. They are conserved in bacteria, plants, and animals. In humans, thirteen members in AQPs family have been identified and are divided into two groups according to transported materials, such as AQP1, AQP2, AQP4, AQP5, or AQP8 are exclusively selective for water, while AQP3, AQP7, AQP9, or AQP10 proposed as aquaglyceroporins can transport water and small neutral solutes such as glycerol. Recently, AQPs such as AQP1, AQP4, or AQP5 were found to be permeable for ion and gas flow (e.g., O2, CO2, or nitric oxide).
Aquaporins are differentially expressed in many types of cells and tissues in the body. AQP0 is abundant in the lens. AQP1 is found in the blood vessels, kidney proximal tubules, eye, and ear. AQP2 is expressed in collecting ducts of kidney and mutations of AQP2 result in diabetes insipidus. AQP3 is expressed in the collecting ducts of kidney, epidermis, urinary, respiratory, and digestive tracts. AQP4 is present in the brain astrocytes, eye, ear, skeletal muscle, stomach parietal cells, and kidney collecting ducts. AQP5 is in the secretory cells such as salivary, lacrimal, and sweat glands and is also expressed in the ear and eye. AQP6 is localized intracellular vesicles in the kidney collecting duct cells. AQP7 is expressed in the adipocytes, testis, and kidney. AQP8 is expressed in the kidney, testis, and liver. AQP9 is present in the liver and leukocytes. AQP10 is expressed in the intestine. The diverse and characteristic distribution of aquaporins in the body suggests their important and specific roles in each organ. Apart from their physiologic role, few studies showed that AQPs were closely associated with cancer biological functions and expressed in more than twenty human cancer cell types. AQPs expression is positively correlated with tumor types, grades, proliferation, migration, angiogenesis, or tumor-associated edema which can be considered as diagnostic and therapeutic targets in anticancer treatment. AQP1 was up-regulated in lung adenocarcinoma, and inhibition of AQP1 expression can inhibit tumor cell invasion, which thereby proposed as the prognostic index and therapeutic target for lung cancer. The expression of AQP5 is reported in tumors such as gastric, pulmonary, ovarian, pancreatic, and colorectal cancer. Recent studies reported the expression of AQP3 in several cancers such as skin, lung, and prostate. The expression of AQP3 and AQP5 was reported in various types of oral cancer. Recently, the expression of AQP3 was reported on tumor cells of tongue cancer and its important role on cell growth.
 Few studies reported about the exact role of AQP3 on the cell growth of squamous cell carcinomas (SCCs) such as esophageal or lingual cancers. The present review overviews AQPs structures, AQPs expression in normal and tumor tissues, AQPs functions and specific roles in cancer development, and potential AQPs-target anticancer drugs.
Kusayama et al. studied the expression of AQP3 in tumor tissues and cell lines along with the role of cell adhesion and inhibition of cell growth and found that the expression was statistically significant in tumor areas than in nontumor areas. Inhibition of AQP3 inhibits cell adhesion and cell growth by inhibiting the integrins α5 and β1 in oral SCC (OSCC) and inhibition of AQP3 by AQP3-small interfering RNA (siRNA) showed cell growth suppression through inhibition of focal adhesion kinase-mitogen-activated protein kinase (MAPK) signaling pathway. AQP3 inhibitorAQP3-siRNA was combined with the existing anti-tumor drugs like cisplatin and 5-fluorouracil in KYSE-30 cell lines and showed drastic inhibition of cell growth. Ishimoto et al. investigated the expression of both AQP5 and AQP3 in tongue SCCs tumor tissues and cultured SCC cell lines (SASs). Statistically significant expression of AQP5 and AQP3 was observed immunohistochemically between tumor and nontumor area and in contrast the markers showed positive expression in nontumor areas of malignant salivary gland tumors than tumor areas. Authors also showed the role of aquaporin 5 in inhibition of cell growth in SCC cell lines (SAS, SCCKN, and CA9-22) using AQP5 inhibitor like AQP5-siRNA and pan-AQP inhibitor like CuSO4 by western blot analysis. When SAS was treated with AQP5-siRNA, it also showed the cell growth suppression of SCCs by the knockdown of AQP5 mediated through the inhibition of integrin expression, and then through the inhibition of MAPK signaling pathway through Erk suppression. It was also shown that combined treatment of AQP5-siRNA and AQP3-siRNA, inhibited the cell growth of SAS similarly in comparison to that in each single high concentrate treatment. These results indicate that combination of AQP5-siRNA and AQP3-siRNA shows additive effect, but not synergetic, on the suppression of SCC growth. Matsuo and Kawano investigated the immunohistochemical expression of AQP3 in OSCC and correlated with lymph node metastasis and suggested that decreased AQP3 expression is associated with more aggressive tumor behavior and increased the incidence of lymphatic metastasis. AQP1 was expressed exclusively by a subgroup of aggressive basaloid-like SCCs and AQP5 was expressed in samples with the lack of expression of p16 and Bcl-2 with a poor clinical outcome in the study conducted by Lehnerdt et al. Liu et al.'s study showed overexpression of AQP3 and AQP5 in esophageal SCC patients using immunohistochemical staining which were significantly correlated with advanced invasion depth, aggressive lymph node status, and positive distant metastasis. With the understanding of the mechanism of AQP's through the studies, many AQPs-target inhibitors have been developed to damage tumor cells. However, further researches were required to verify the efficiency and safety of these AQPs-target inhibitors in clinical therapy.
The authors would like to acknowledge Dr. Kuniaki Takata, Ph.D., D.M. Sc., President, Gunma Prefectural College of Health Sciences, Gunma, Japan for providing their article matter in writing the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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