Skip to main content

Advertisement

SpringerLink
Log in

Differential Expression of Aquaporins in Cervical Precursor Lesions and Invasive Cervical Cancer

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Objective

Aquaporins (AQPs) are highly expressed in tumor cells of different origins, particularly the aggressive tumors. The aim of this study was to investigate the expression of AQP isoforms during progression of squamous cervical cancer (SCC) and explore their associations with clinicopathologic variables of SCC.

Methods

Expression of AQP isoforms (1, 3, 4, 5, and 8) was detected by immunohistochemistry in 47 SCCs, 37 cervical intraepithelial neoplasia (CIN), and 16 normal cervical tissues. Specific expression of AQP protein in SCC was detected by Western blot. Double immunohistochemistry was used to examine whether AQPs and vascular endothelial growth factor (VEGF) are coexpressed in SCC.

Results

Aquaporin 1 showed higher positivity rate in CIN than in SCC and normal cervical tissues (P <.05). The expression intensity of AQP3, 4, 5, and 8 was higher in SCC than that in normal cervical tissues, respectively (P <.05). The expression of AQP3 and 8 was higher in SCC than that in CIN, respectively (P <.05). The AQP4 expression was higher in CIN than in normal cervical tissues (P <.05). The expression of AQP3 in CIN III was higher than that in CIN I and II (P <.05). There was a significant increase in the expression of AQP1 in stage I than that in stage II (P <.05). Aquaporin 3 showed lower positivity in moderately and well-differentiated tumors compared to that in poorly differentiated tumors (P <.05). Finally, double immunohistochemistry illustrated that AQP1/AQP3/AQP8 and VEGF were coexpressed in SCC.

Conclusions

Different AQP isoforms display specific expression patterns in normal cervical, CIN, and SCC tissues. This and the significant association with the clinicopathologic variables of SCC suggest that AQP isoforms might play different roles in the development of cervical cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. de Freitas AC, Gurgel AP, Chagas BS, Coimbra EC, do Amaral CM. Susceptibility to cervical cancer: an overview. Gynecol Oncol. 2012;126(2):304–311.

    Article  PubMed  Google Scholar 

  2. Einstein MH. Women whose cervical intraepithelial neoplasia has been treated or resolved remain at continued high risk for cervical cancer. Evid Based Med. 2013;18(5):190–191.

    Article  PubMed  Google Scholar 

  3. Verkman AS, Hara-Chikuma M, Papadopoulos MC. Aquaporins—new players in cancer biology. J Mol Med. 2008;86(5):523–529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yang JH, Shi YF, Chen XD, Qi WJ. The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites formation. Int J Gynecol Cancer. 2006;16(suppl 1):400–405.

    Article  CAS  PubMed  Google Scholar 

  5. Pan H, Sun CC, Zhou CY, Huang HF. Expression of aquaporin-1 in normal, hyperplasic, and carcinomatous endometria. Int J Gynaecol Obstet. 2008;101(3):239–244.

    Article  CAS  PubMed  Google Scholar 

  6. Moon C, Soria JC, Jang SJ, et al. Involvement of aquaporins in colorectal carcinogenesis. Oncogene. 2003;22(43):6699–6703.

    Article  CAS  PubMed  Google Scholar 

  7. Wang J, Tanji N, Kikugawa T, Shudou M, Song X, Yokoyama M. Expression of aquaporin 3 in the human prostate. Int J Urol. 2007;14(12):1088–1092.

    Article  CAS  PubMed  Google Scholar 

  8. Liu YL, Matsuzaki T, Nakazawa T, et al. Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol. 2007;38(1):171–178.

    Article  CAS  PubMed  Google Scholar 

  9. 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(1):326–332.

    Article  CAS  PubMed  Google Scholar 

  10. Dua RK, Devi BI, Yasha TC. Increased expression of Aquaporin-4 and its correlation with contrast enhancement and perilesional edema in brain tumors. Br J Neurosurg. 2010;24(4):454–459.

    Article  PubMed  Google Scholar 

  11. Kang SK, Chae YK, Woo J, et al. Role of human aquaporin 5 in colorectal carcinogenesis. Am J Pathol. 2008;173(2):518–525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett. 2007;250(1):36–46.

    Article  CAS  PubMed  Google Scholar 

  13. Anderson J, Brown N, Mahendroo MS, Reese J. Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening. Endocrinology. 2006;147(1):130–140.

    Article  CAS  PubMed  Google Scholar 

  14. Shi YH, Chen R, Talafu T, Nijiati R, Lalai S. Significance and expression of aquaporin 1, 3, 8 in cervical carcinoma in Xinjiang Uygur women of China. Asian Pac J Cancer Prev. 2012;13(5):1971–1975.

    Article  PubMed  Google Scholar 

  15. Zhang T, Zhao C, Chen D, Zhou Z. Overexpression of AQP5 in cervical cancer: correlation with clinicopathological features and prognosis. Med Oncol. 2012;29(3):1998–2004.

    Article  CAS  PubMed  Google Scholar 

  16. Pandya NM, Dhalla NS, Santani DD. Angiogenes is a new target for future therapy. Vascul Pharmaco. 2006;44(5):265–274.

    Article  CAS  Google Scholar 

  17. Chaudary N, Milosevic M, Hill RP. Suppression of vascular endothelial growth factor receptor 3 (VEGFR3) and vascular endothelial growth factor C (VEGFC) inhibits hypoxia-induced lymph node metastases in cervix cancer. Gynecol Oncol. 2011;123(2):393–400.

    Article  CAS  PubMed  Google Scholar 

  18. Wang P, Ni RY, Chen MN, Mou KJ, Mao Q, Liu YH. Expression of aquaporin-4 in human supratentorial meningiomas with peritumoral brain edema and correlation of VEGF with edema formation. Genet Mol Res. 2011;10(3):2165–2171.

    Article  CAS  PubMed  Google Scholar 

  19. Hollborn M, Vogler S, Reichenbach A, Wiedemann P, Bringmann A, Kohen L. Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in retinal pigment epithelial cells: involvement of NFAT5. Mol Vis. 2015;21:360–377.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Lin F, Pan LH, Ruan L, et al. Differential expression of HIF-1α, AQP-1, and VEGF under acute hypoxic conditions in the non-ventilated lung of a one-lung ventilation rat model. Life Sci. 2015;124:50–55.

    Article  CAS  PubMed  Google Scholar 

  21. Weidner N. Current pathologic methods for measuring intratumoral microvessel density with breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36(2):169–180.

    Article  CAS  PubMed  Google Scholar 

  22. Kahl P, Gullotti L, Heukamp LC, et al. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006;66(23):11341–11347.

    Article  CAS  PubMed  Google Scholar 

  23. Chen J, Zheng H, Bei JX, et al. Genetic structure of the Han Chinese population revealed by genome-wide SNP variation. Am J Hum Genet. 2009;85(6):775–785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ji C, Cao C, Lu S, et al. Curcumin attenuates EGF-induced AQP3 up- regulation and cell migration in human ovarian cancer cells. Cancer Chemother Pharmacol. 2008;62(5):857–865.

    Article  CAS  PubMed  Google Scholar 

  25. Xu H, Zhang Y, Wei W, Shen L, Wu W. Differential expression of aquaporin-4 in human gastric normal and cancer tissues. Gastroenterol Clin Biol. 2009;33(1 pt 1):72–76.

    Article  CAS  PubMed  Google Scholar 

  26. Shi Z, Zhang T, Luo L, et al. Aquaporins in human breast cancer: identification and involvement in carcinogenesis of breast cancer. J Surg Oncol. 2012;106(3):267–72.

    Article  CAS  PubMed  Google Scholar 

  27. Yang JH, Shi YF, Cheng Q, Deng L. Expression and localization of aquaporin-5 in the epithelial ovarian tumors. Gynecol Oncol. 2006;100(2):294–299.

    Article  CAS  PubMed  Google Scholar 

  28. Fischer H, Stenling R, Rubio C, Lindblom A. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol. 2001;1:1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shi YH, Rehemu N, Ma H, Tuokan T, Chen R, Suzuke L. Increased migration and local invasion potential of SiHa cervical cancer cells expressing aquaporin 8. Asian Pac J Cancer Prev. 2013;14(3):1825–1828.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang, 325027, China

    Qi Shen MD, Wenjing Lin MD, Hui Luo MD, Chuchu Zhao MD, Huihui Cheng MD, Wenxiao Jiang MD & Xueqiong Zhu MD, PhD

Authors
  1. Qi Shen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenjing Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hui Luo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chuchu Zhao MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huihui Cheng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenxiao Jiang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xueqiong Zhu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xueqiong Zhu MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, Q., Lin, W., Luo, H. et al. Differential Expression of Aquaporins in Cervical Precursor Lesions and Invasive Cervical Cancer. Reprod. Sci. 23, 1551–1558 (2016). https://doi.org/10.1177/1933719116646202

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116646202

Keywords

Search

Navigation