Claudin-1, but not claudin-4, exhibits differential expression patterns between well- to moderately-differentiated and poorly-differentiated gastric adenocarcinoma

Tokuhara,Yasunori; Morinishi,Tatsuya; Matsunaga,Toru; Ohsaki,Hiroyuki; Kushida,Yoshio; Haba,Reiji; Hirakawa,Eiichiro

doi:10.3892/ol.2015.3208

Claudin-1, but not claudin-4, exhibits differential expression patterns between well- to moderately-differentiated and poorly-differentiated gastric adenocarcinoma

Authors:
- Yasunori Tokuhara
- Tatsuya Morinishi
- Toru Matsunaga
- Hiroyuki Ohsaki
- Yoshio Kushida
- Reiji Haba
- Eiichiro Hirakawa
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Affiliations: Laboratory of Pathology, Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa 761‑0123, Japan, Department of Diagnostic Pathology, University Hospital, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan, Department of Medical Technology, Ehime Prefectural University of Health Sciences, Ehime 791‑2101, Japan
Published online on: May 14, 2015 https://doi.org/10.3892/ol.2015.3208
Pages: 93-98
Copyright: © Tokuhara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Claudins are members of a large family of transmembrane proteins, which are essential in the formation of tight junctions and have previously been associated with the process of tumor progression. Studies have reported the aberrant expression of claudin‑1 and claudin‑4 in numerous types of cancer. The present study aimed to investigate the expression of claudin‑1 and claudin‑4 in gastric adenocarcinoma tissue. Surgically resected gastric adenocarcinoma tissue specimens were obtained from 94 patients. Protein expression levels of claudin‑1 and claudin‑4 were determined using immunohistochemical staining; the association between claudin‑1 or claudin‑4 expression and various clinicopathological parameters were then analyzed. In gastric adenocarcinoma specimens, the expression rates of claudin‑1 and claudin‑4 were 43.6 and 87.2%, respectively. Claudin‑1 expression demonstrated a significant correlation with histological type (P<0.01) and was significantly higher in well‑ to moderately‑differentiated gastric adenocarcinomas compared with poorly‑differentiated tumors. However, no correlation was observed between claudin‑4 expression in adenocarcinoma and clinicopathological parameters. In conclusion, downregulation of claudin‑1 expression in poorly‑differentiated gastric adenocarcinoma may be involved in the biological transformation of tumors. The present findings suggested that claudin‑1 may be an important protein associated with histological type and therefore may have potential for use as a prognostic marker for gastric adenocarcinoma. Further studies are required to elucidate the precise mechanism of claudin expression and its involvement in tumor progression.

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1	Yamamoto S: Stomach cancer incidence in the world. Jpn J Clin Oncol. 31:4712001.PubMed/NCBI
2	Ahn YO, Park BJ, Yoo KY, et al: Incidence estimation of stomach cancer among Koreans. J Korean Med Sci. 6:7–14. 1991. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
4	Correa P: Human gastric carcinogenesis: A multistep and multifactorial process - First American Cancer Society award lecture on cancer epidemiology and prevention. Cancer Res. 52:6735–6740. 1992.PubMed/NCBI
5	Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI
6	Thiery JP: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 15:740–746. 2003. View Article : Google Scholar : PubMed/NCBI
7	Matter K and Balda MS: Signalling to and from tight junctions. Nat Rev Mol Cell Biol. 4:225–236. 2003. View Article : Google Scholar : PubMed/NCBI
8	Mitic LL, Van Itallie CM and Anderson JM: Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol. 279:G250–G254. 2000.PubMed/NCBI
9	Tsukita S, Furuse M and Itoh M: Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2:285–293. 2001. View Article : Google Scholar : PubMed/NCBI
10	Mitic LL and Anderson JM: Molecular architecture of tight junctions. Annu Rev Physiol. 60:121–142. 1998. View Article : Google Scholar : PubMed/NCBI
11	Martin TA and Jiang WG: Tight junctions and their role in cancer metastasis. Histol Histopathol. 16:1183–1195. 2001.PubMed/NCBI
12	Langbein L, Pape UF, Grund C, et al: Tight junction-related structures in the absence of a lumen: occludin, claudins and tight junction plaque proteins in densely packed cell formations of stratified epithelia and squamous cell carcinomas. Eur J Cell Biol. 82:385–400. 2003. View Article : Google Scholar : PubMed/NCBI
13	Itoh M and Bissell MJ: The organization of tight junctions in epithelia: implications for mammary gland biology and breast tumorigenesis. J Mammary Gland Biol Neoplasia. 8:449–462. 2003. View Article : Google Scholar : PubMed/NCBI
14	Turksen K and Troy TC: Barriers built on claudins. J Cell Sci. 117:(12 Pt). 2435–2447. 2004. View Article : Google Scholar : PubMed/NCBI
15	Soini Y, Tommola S, Helin H and Martikainen P: Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch. 448:52–58. 2006. View Article : Google Scholar : PubMed/NCBI
16	Jung H, Jun KH, Jung JH, Chin HM and Park WB: The expression of claudin-1, claudin-2, claudin-3 and claudin-4 in gastric cancer tissue. J Surg Res. 167:e185–e191. 2011. View Article : Google Scholar : PubMed/NCBI
17	Wu YL, Zhang S, Wang GR and Chen YP: Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion. World J Gastroenterol. 14:4943–4948. 2008. View Article : Google Scholar : PubMed/NCBI
18	Ohtani S, Terashima M, Satoh J, et al: Expression of tight-junction-associated proteins in human gastric cancer: downregulation of claudin-4 correlates with tumor aggressiveness and survival. Gastric Cancer. 12:43–51. 2009. View Article : Google Scholar : PubMed/NCBI
19	Resnick MB, Gavilanez M, Newton E, et al: Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Hum Pathol. 36:886–892. 2005. View Article : Google Scholar : PubMed/NCBI
20	Michl P, Barth C, Buchholz M, et al: Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res. 63:6265–6271. 2003.PubMed/NCBI
21	Agarwal R, D'Souza T and Morin PJ: Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 65:7378–7385. 2005. View Article : Google Scholar : PubMed/NCBI
22	Japanese Gastric Cancer Association, . Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 14:101–112. 2011. View Article : Google Scholar : PubMed/NCBI
23	Sano T and Aiko T: New Japanese classifications and treatment guidelines for gastric cancer: Revision concepts and major revised points. Gastric Cancer. 14:97–100. 2011. View Article : Google Scholar : PubMed/NCBI
24	Ikenouchi J, Matsuda M, Furuse M and Tsukita S: Regulation of tight junctions during the epithelium-mesenchyme transition: Direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci. 116:1959–1967. 2003. View Article : Google Scholar : PubMed/NCBI
25	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
26	Gottardi CJ, Arpin M, Fanning AS and Louvard D: The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Proc Natl Acad Sci USA. 93:10779–10784. 1996. View Article : Google Scholar : PubMed/NCBI
27	Jechlinger M, Grunert S, Tamir IH, et al: Expression profiling of epithelial plasticity in tumor progression. Oncogene. 22:7155–7169. 2003. View Article : Google Scholar : PubMed/NCBI
28	Tsukita S and Furuse M: Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol. 149:13–16. 2000. View Article : Google Scholar : PubMed/NCBI
29	Hoevel T, Macek R, Swisshelm K and Kubbies M: Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. Int J Cancer. 108:374–383. 2004. View Article : Google Scholar : PubMed/NCBI
30	Matsuda Y, Semba S, Ueda J, et al: Gastric and intestinal claudin expression at the invasive front of gastric carcinoma. Cancer Sci. 98:1014–1019. 2007. View Article : Google Scholar : PubMed/NCBI
31	Resnick MB, Konkin T, Routhier J, Sabo E and Pricolo VE: Claudin-1 is a strong prognostic indicator in stage II colonic cancer: A tissue microarray study. Mod Pathol. 18:511–518. 2005. View Article : Google Scholar : PubMed/NCBI
32	Satake S, Semba S, Matsuda Y, et al: Cdx2 transcription factor regulates claudin-3 and claudin-4 expression during intestinal differentiation of gastric carcinoma. Pathol Int. 58:156–163. 2008. View Article : Google Scholar : PubMed/NCBI
33	Xin S, Huixin C, Benchang S, et al: Expression of Cdx2 and claudin-2 in the multistage tissue of gastric carcinogenesis. Oncology. 73:357–365. 2007. View Article : Google Scholar : PubMed/NCBI
34	Krämer F, White K, Kubbies M, Swisshelm K and Weber BH: Genomic organization of claudin-1 and its assessment in hereditary and sporadic breast cancer. Hum Genet. 107:249–256. 2000. View Article : Google Scholar : PubMed/NCBI
35	Tokés AM, Kulka J, Paku S, et al: Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: A research study. Breast Cancer Res. 7:R296–R305. 2005. View Article : Google Scholar : PubMed/NCBI
36	Kominsky SL, Argani P, Korz D, et al: 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
37	Liebner S, Fischmann A, Rascher G, et al: Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 100:323–331. 2000. View Article : Google Scholar : PubMed/NCBI
38	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
39	Lauren P: The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 64:31–49. 1965.PubMed/NCBI
40	Ming SC: Gastric carcinoma. A pathobiological classification. Cancer. 39:2475–2485. 1977. View Article : Google Scholar : PubMed/NCBI
41	Sugano H, Nakamura K and Kato Y: Pathological studies of human gastric cancer. Acta Pathol Jpn. 32:(Suppl 2). 329–347. 1982.PubMed/NCBI
42	Adachi Y, Yasuda K, Inomata M, Sato K, Shiraishi N and Kitano S: Pathology and prognosis of gastric carcinoma: Well versus poorly differentiated type. Cancer. 89:1418–1424. 2000. View Article : Google Scholar : PubMed/NCBI
43	Park JM, Jang YJ, Kim JH, et al: Gastric cancer histology: Clinicopathologic characteristics and prognostic value. J Surg Oncol. 98:520–525. 2008. View Article : Google Scholar : PubMed/NCBI
44	Zhu JL, Gao P, Wang ZN, et al: Clinicopathological significance of claudin-4 in gastric carcinoma. World J Surg Oncol. 11:1502013. View Article : Google Scholar : PubMed/NCBI
45	Kuo WL, Lee LY, Wu CM, et al: Differential expression of claudin-4 between intestinal and diffuse-type gastric cancer. Oncol Rep. 16:729–734. 2006.PubMed/NCBI
46	Lee SK, Moon J, Park SW, Song SY, Chung JB and Kang JK: Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma. Oncol Rep. 13:193–199. 2005.PubMed/NCBI
47	Kominsky SL, Vali M, Korz D, et al: Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins claudin 3 and 4. Am J Pathol. 164:1627–1633. 2004. View Article : Google Scholar : PubMed/NCBI