Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Yang,Luoluo; Sun,Xun; Meng,Xiangwei

doi:10.3892/mmr.2018.9122

Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Authors:
- Luoluo Yang
- Xun Sun
- Xiangwei Meng
View Affiliations

Affiliations: Department of Gastroenterology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pathology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: June 1, 2018 https://doi.org/10.3892/mmr.2018.9122
Pages: 1271-1278
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Numerous genetic alterations associated with cancer progression have the potential to serve as biomarkers for the early diagnosis of cancer. Numerous studies have suggested that claudin proteins, which are the primary components of tight junction structures, are associated with the regulation of cell polarity and cell differentiation. To investigate the expression profiles of the tight junction proteins claudin‑2, ‑5, ‑7 and ‑8 in gastric carcinoma, immunohistochemical analysis, western blotting and reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression profiles of these claudin proteins in gastric carcinoma tissues and in homologous non‑neoplastic mucosal tissues. According to the present study, the expression levels of claudin‑7 and claudin‑8 were downregulated, while the expression of claudin‑5 was upregulated in gastric carcinoma tissues compared with in non‑neoplastic mucosal tissues. Additionally, no notable difference was observed between claudin‑2 expression in gastric carcinoma tissues and non‑neoplastic mucosae. Correlations between claudin‑7 and ‑8 expression and lymphatic metastasis in gastric carcinoma tissues were additionally reported. In summary, the present study revealed the distinct expression profiles of claudin‑5, ‑7 and ‑8 in non‑neoplastic mucosal tissues and gastric carcinoma tissues. Furthermore, the expression of these claudin proteins was highly associated with metastatic progression and prognosis in patients with gastric carcinoma, and had predictive value for the metastasis and survival of patients with gastric carcinoma.

View Figures

View References

1	Dejana E: Endothelial cell-cell junctions: Happy together. Nat Rev Mol Cell Biol. 5:261–270. 2004. View Article : Google Scholar : PubMed/NCBI
2	Brandner JM, Haftek M and Niessen CM: Adherens junctions, desmosomes and tight junctions in epidermal barrier function. Open Dermatol J. 4:14–20. 2010. View Article : Google Scholar
3	Förster C: Tight junctions and the modulation of barrier function in disease. Histochem Cell Biol. 130:55–70. 2008. View Article : Google Scholar : PubMed/NCBI
4	Niessen CM: Tight junctions/adherens junctions: Basic structure and function. J Invest Dermatol. 127:2525–2532. 2007. View Article : Google Scholar : PubMed/NCBI
5	Martin TA and Jiang WG: Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta. 1788:872–891. 2009. View Article : Google Scholar : PubMed/NCBI
6	Schneeberger EE and Lynch RD: The tight junction: A multifunctional complex. Am J Physiol Cell Physiol. 286:C1213–C1228. 2004. View Article : Google Scholar : PubMed/NCBI
7	Zhang GH, Wu L and Yu GY: Tight junctions and paracellular fluid and ion transport in salivary glands. Chin J Dent Res. 16:13–46. 2013.PubMed/NCBI
8	Van Itallie CM and Anderson JM: The molecular physiology of tight junction pores. Physiology (Bethesda). 19:331–338. 2004.PubMed/NCBI
9	Coradini D, Casarsa C and Oriana S: Epithelial cell polarity and tumorigenesis: New perspectives for cancer detection and treatment. Acta Pharmacol Sin. 32:552–564. 2011. View Article : Google Scholar : PubMed/NCBI
10	Lee M and Vasioukhin V: Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. J Cell Sci. 121:1141–1150. 2008. View Article : Google Scholar : PubMed/NCBI
11	Morin PJ: Claudin proteins in human cancer: Promising new targets for diagnosis and therapy. Cancer Res. 65:9603–9606. 2005. View Article : Google Scholar : PubMed/NCBI
12	Tabariès S and Siegel PM: The role of claudins in cancer metastasis. Oncogene. 36:1176–1190. 2017. View Article : Google Scholar : PubMed/NCBI
13	González-Mariscal L, Tapia R and Chamorro D: Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta. 1778:729–756. 2008. View Article : Google Scholar : PubMed/NCBI
14	Oliveira S and Morgado-Díaz JA: Claudins: Multifunctional players in epithelial tight junctions and their role in cancer. Cell Mol Life Sci. 64:17–28. 2007. View Article : Google Scholar : PubMed/NCBI
15	Morita K, Furuse M, Fujimoto K and Tsukita S: Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci. 96:511–516. 1999. View Article : Google Scholar : PubMed/NCBI
16	Krause G, Winkler L, Mueller SL, Haseloff RF, Piontek J and Blasig IE: Structure and function of claudins. Biochim Biophy Acta. 1778:631–645. 2008. View Article : Google Scholar
17	Elkouby-Naor L and Ben-Yosef T: Functions of claudin tight junction proteins and their complex interactions in various physiological systems. Int Rev Cell Mol Biol. 279:1–32. 2010. View Article : Google Scholar : PubMed/NCBI
18	Findley MK and Koval M: Regulation and roles for claudin-family tight junction proteins. IUBMB Life. 61:431–437. 2009. View Article : Google Scholar : PubMed/NCBI
19	Lal-Nag M and Morin PJ: The claudins. Genome Biol. 10:2352009. View Article : Google Scholar : PubMed/NCBI
20	Ikari A, Sato T, Watanabe R, Yamazaki Y and Sugatani J: Increase in claudin-2 expression by an EGFR/MEK/ERK/c-Fos pathway in lung adenocarcinoma A549 cells. Biochim Biophy Acta. 1823:1110–1118. 2012. View Article : Google Scholar
21	Itoh M, Furuse M, Morita K, Kubota K, Saitou M and Tsukita S: Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 147:1351–1363. 1999. View Article : Google Scholar : PubMed/NCBI
22	D'Souza T, Agarwal R and Morin PJ: Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells. J Biol Chem. 280:26233–26240. 2005. View Article : Google Scholar : PubMed/NCBI
23	D'Souza T, Indig FE and Morin PJ: Phosphorylation of claudin-4 by PKCepsilon regulates tight junction barrier function in ovarian cancer cells. Exp Cell Res. 313:3364–3375. 2007. View Article : Google Scholar : PubMed/NCBI
24	Kominsky SL: Claudins: Emerging targets for cancer therapy. Expert Rev Mol Med. 8:1–11. 2006. View Article : Google Scholar : PubMed/NCBI
25	Furuse M and Tsukita S: Claudins in occluding junctions of humans and flies. Trends Cell Biol. 16:181–188. 2006. View Article : Google Scholar : PubMed/NCBI
26	Günzel D and Alan S: Claudins and the modulation of tight junction permeability. Physiol Rev. 93:525–569. 2013. View Article : Google Scholar : PubMed/NCBI
27	Ouban A and Ahmed AA: Claudins in human cancer: A review. Histol Histopathol. 25:83–90. 2010.PubMed/NCBI
28	Osanai M, Takasawa A, Murata M and Sawada N: Claudins in cancer: Bench to bedside. Pflugers Arch. 469:55–67. 2017. View Article : Google Scholar : PubMed/NCBI
29	Kwon MJ: Emerging roles of claudins in human cancer. Int J Mol Sci. 14:18148–18180. 2013. View Article : Google Scholar : PubMed/NCBI
30	Katai H, Yoshimura K, Maruyama K, Sasako M and Sano T: Evaluation of the New International Union Against Cancer TNM staging for gastric carcinoma. Cancer. 88:1796–1800. 2000. View Article : Google Scholar : PubMed/NCBI
31	Pan XY, Wang B, Che YC, Weng ZP, Dai HY and Peng W: Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue. Int J Gynecol Cancer. 17:233–241. 2007. View Article : Google Scholar : PubMed/NCBI
32	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
33	Yang Y, Yang H, McNutt MA, Xiong F, Nie X, Li L and Zhou R: LAPTM4B overexpression is an independent prognostic marker in ovarian carcinoma. Oncol Rep. 20:1077–1083. 2008.PubMed/NCBI
34	Lin Z, Zhang X, Liu Z, Liu Q, Wang L, Lu Y, Liu Y, Wang M, Yang M, Jin X and Quan C: The distinct expression patterns of claudin-2, −6, and −11 between human gastric neoplasms and adjacent non-neoplastic tissues. Diagn Pathol. 8:1332013. View Article : Google Scholar : PubMed/NCBI
35	Lu Z: Functions of claudin-7 in human lung cancer. 2012.
36	Hewitt KJ, Agarwal R and Morin PJ: The claudin gene family: Expression in normal and neoplastic tissues. BMC Cancer. 6:1862006. View Article : Google Scholar : PubMed/NCBI
37	Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP and Sukumar S: Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene. 22:2021–2033. 2003. View Article : Google Scholar : PubMed/NCBI
38	Singh AB, Sharma A and Dhawan P: Claudin family of proteins and cancer: An overview. J Oncol. 2010:5419572010. View Article : Google Scholar : PubMed/NCBI
39	Swisshelm K, Macek R and Kubbies M: Role of claudins in tumorigenesis. Adv Drug Deliv Rev. 57:919–928. 2005. View Article : Google Scholar : PubMed/NCBI
40	Webb PG, Spillman MA and Baumgartner HK: Claudins play a role in normal and tumor cell motility. BMC Cell Biol. 14:192013. View Article : Google Scholar : PubMed/NCBI
41	Rangel LB, Agarwal R, D'Souza T, Pizer ES, Alò PL, Lancaster WD, Gregoire L, Schwartz DR, Cho KR and Morin PJ: Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. Clin Cancer Res. 9:2567–2575. 2003.PubMed/NCBI
42	Szász MA: Claudins as prognostic factors of breast cancer. Magy Onkol. 56:209–212. 2012.(In Hungarian). PubMed/NCBI
43	Zhang X, Ruan Y, Li Y, Lin D, Liu Z and Quan C: Expression of apoptosis signal-regulating kinase 1 is associated with tight junction protein claudin-6 in cervical carcinoma. Int J Clin Exp Pathol. 8:5535–5541. 2015.PubMed/NCBI
44	Wang H and Yang X: The expression patterns of tight junction protein claudin-1, −3, and −4 in human gastric neoplasms and adjacent non-neoplastic tissues. Int J Clin Exp Pathol. 8:881–887. 2015.PubMed/NCBI
45	Zhu J and Wang R, Cao H, Zhang H, Xu S, Wang A, Liu B, Wang Y and Wang R: Expression of claudin-5, −7, −8 and −9 in cervical carcinoma tissues and adjacent non-neoplastic tissues. Int J Clin Exp Pathol. 8:9479–9486. 2015.PubMed/NCBI
46	Huang J, Li J, Qu Y, Zhang J, Zhang L, Chen X, Liu B and Zhu Z: The expression of claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer. Int J Oncol. 44:1293–1301. 2014. View Article : Google Scholar : PubMed/NCBI
47	Zhu JL, Gao P, Wang ZN, Song YX, Li AL, Xu YY, Wang MX and Xu HM: Clinicopathological significance of claudin-4 in gastric carcinoma. World J Surg Oncol. 11:1502013. View Article : Google Scholar : PubMed/NCBI
48	Gao M, Li W, Wang H and Wang G: The distinct expression patterns of claudin-10, −14, −17 and E-cadherin between adjacent non-neoplastic tissues and gastric cancer tissues. Diagn Pathol. 8:2052013. View Article : Google Scholar : PubMed/NCBI
49	Lu Y, Jing J, Sun L, Gong Y, Chen M, Wang Z, Sun M and Yuan Y: Expression of claudin-11, −23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer. PLoS One. 12:e01744762017. View Article : Google Scholar : PubMed/NCBI