Elsevier

Gynecologic Oncology

Volume 100, Issue 2, February 2006, Pages 294-299
Gynecologic Oncology

Expression and localization of aquaporin-5 in the epithelial ovarian tumors

https://doi.org/10.1016/j.ygyno.2005.08.054Get rights and content

Abstract

Objective.

To investigate the expression and localization of aquaporin-5 (AQP5) in epithelial ovarian tumors and its clinic significance.

Methods.

The expression of AQP5 protein and mRNA in 65 cases epithelial ovarian tumors and 13 cases normal tissue were measured by immunohistochemical technique, Western blotting and RT-PCR, respectively.

Results.

AQP5 is mainly localized in the basolateral membranes of benign tumor cells, the apical and basolateral membrane of borderline cells and scattered in the membrane of malignant cells and almost no or weak staining in normal ovarian epithelium. The AQP5 expression in ovarian malignant and borderline tumors was significantly higher than that of benign tumors (P < 0.05) and normal tissue (P < 0.05). Of all the epithelial ovarian malignant tumors, the AQP5 expression in cases with ascites volume more than 1000 ml was higher than that of ascites volume less than 500 ml (P < 0.05). Increased AQP5 protein level was associated with lymph node metastasis (P < 0.05). There is a positive correlation between ascites amount and the expression of AQP5 protein and mRNA (P < 0.05), as well as lymph node metastasis and the expression of AQP5 protein and mRNA (P < 0.05). The AQP5 expression was not related with FIGO stage, grade and histological type (P > 0.05).

Conclusion.

The data suggest that overexpression of AQP5 play an important role in tumorigenesis of epithelial ovarian tumors, which may be related to the ascites formation of ovarian carcinoma.

Introduction

Ovarian carcinoma represents the leading cause of death from gynecologic malignancy [1]. Due to the lack of reliable tumor marker and vague or absent symptoms in the early stages of the diseases, 70% of patients initially present with advanced disease [2]. As ovarian cancer progresses, the peritoneal cavity of patients frequently accumulates malignant ascites fluid. There were two views held on the mechanisms underlying malignant ascites formation. Several authors had suggested that an increase in capillary permeability to osmotically active proteins in the tumor and/or surrounding peritoneal tissues led to excess peritoneal fluid accumulation [3], [4]. However, Feldman and Coates proposed that obliteration of the diaphragmatic lymphatics by tumor cells caused a reduction in absorption of protein normally filtered across peritoneal capillaries, thus resulting in ascites formation [5], [6]. Moreover, Nagy [7], [8] elucidated that vascular permeability factor (VPF) overexpression was an initiating event in the pathogenesis of malignant ascites formation. However, the relationship between the water permeability of ovarian malignant cells and ascites formation is unclear by now.

Changes in water permeability across biological membranes imply the existence of water channels. Identification of molecules of water channels has recently shown that they are members of a new family of membrane proteins termed aquaporins (AQPs) [9]. The family of mammalian AQPs consists of 11 members, AQP0–10, each with a distinct tissue, and it was assumed that alteration in AQP expression or function can be rate-limiting for water transporting certain membranes [9], [10], [11]. AQP5 is a 27-kDa protein that was first cloned from the salivary gland and is known as an exocrine-type water channel with a unique tissue expression [12]. By experiments using Northern blot analysis and in situ hybridization, strong expression of AQP5 mRNA was shown in many exocrine gland tissues, i.e., the salivary gland, eye, lacrimal gland, lung and trachea [12], [13]. AQP5 was thought to play a fundamental role in the water movement for the formation of saliva, tears and other secretions [9]. Recent report had shown that the expression of AQP5 was induced in early-stage disease and maintained through the stages of colon cancer. These findings demonstrate that the expression of AQP5 is associated with an early stage of colorectal cancer development, which suggests that it may be prior to tumorigenesis [14]. However, the distribution and expression of APQ5 in ovarian epithelial tumors and its clinic significance are unclear, which have not been reported until now.

Based upon above observation, we believed that AQP5 play a potential role in ovarian carcinogenesis and ascites formation. To test this hypothesis, we used immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) to measure the expression and localization of AQP5 in ovarian epithelial tumors and normal tissue. Our results provide a clear and novel example of AQP5 expression and localization during ovarian carcinogenesis.

Section snippets

Tissue specimens

From February to November 2004, specimen of 65 primary ovarian epithelial tumors (15 benign, 15 borderline and 35 malignant) and 13 normal ovary tissue with uterine myoma were collected from patients (age ranged from 17 to 70, with a median at 49 years) who underwent surgical resection of the ovaries at Women's Hospital of Zhejiang University, Hangzhou, China. Information about FIGO stage, histological type, grade and lymph node metastasis was taken from the patients' clinical records. Of 15

Immunohistochemical localization of AQP5

Immunohistochemical study showed that AQP5 protein was mainly localized in epithelial ovarian tumor cells. Different localization of AQP5 was observed among benign, borderline and malignant tumor cells. AQP5 protein was expressed in the basolateral plasma membranes of benign tumor cells, both the apical and basolateral membrane of borderline cells and scattered in the membranes of malignant cells and almost no or weak staining in normal ovarian epithelium (Figs. 1A–D).

Western blotting analysis

The anti-AQP5 antibody

Discussion

Previous studies found that AQP5 was localized in the apical and lateral membrane of acinar cells and secretory cells, with no signal for AQP5 detectable in the basal membrane [15], [16], [17], [18], [19]. Murdiastuti [20] reported that the submandibular gland of low expressers showed similar results as those reported previously. In the high expressers, AQP5 protein was localized not only in the apical and lateral membrane, but also in the basal membrane of acinar cells. In the present study,

Acknowledgments

The authors thank Dr. Xinchao Wang for his critical review of the manuscript and Huaizeng Chen for helpful technical support.

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