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Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

  • Alikanoglu, Arsenal Sezgin (Department of Pathology, Gaziantep Medical Park Hospital) ;
  • Gunduz, Seyda (Department of Medical Oncology, Gaziantep Medical Park Hospital) ;
  • Demirpence, Ozlem (Department of Biochemistry, Cumhuriyet University Medical Faculty) ;
  • Suren, Dinc (Department of Pathology, Gaziantep Medical Park Hospital) ;
  • Gunduz, Umut Riza (Department of General Surgery, Antalya Education and Research Hospital) ;
  • Sezer, Cem (Department of Pathology, Gaziantep Medical Park Hospital) ;
  • Yildiz, Mustafa (Department of Medical Oncology, Gaziantep Medical Park Hospital) ;
  • Yildirim, Mustafa (Department of Medical Oncology, Gaziantep Medical Park Hospital)
  • Published : 2015.06.03

Abstract

Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

Keywords

References

  1. Agarwal R, Mori Y, Cheng Y, et al (2009). Silencing of claudin-11 is associated with increased invasiveness of gastric cancer cells. PLoS One, 4, 8002. https://doi.org/10.1371/journal.pone.0008002
  2. Boireau S, Buchert M, Samuel MS, et al (2007). DNAmethylation- dependent alterationsof claudin-4 expression in human bladder carcinoma. Carcinogenesis, 28, 246-58. https://doi.org/10.1093/carcin/bgl120
  3. Borka K, Kaliszky P, Szabo E, et al (2007). Claudin expression in pancreatic endocrine tumors as compared with ductal adenocarcinomas. Virchows Arch, 450, 549-57. https://doi.org/10.1007/s00428-007-0406-7
  4. Bornholdt J, Friis S, Godiksen S, et al (2011). The level of Claudin-7 is reduced as an early event in colorectal carcinogenesis. BMC Cancer, 11, 65. https://doi.org/10.1186/1471-2407-11-65
  5. Bunthot S, Obchoei S, Kraiklang R, et al (2012). Overexpression of claudin-4 in cholangiocarcinoma tissues and its possible role in tumor metastasis. Asian Pac J Cancer Prev, 13, 71-6.
  6. Comper F, Antonello D, Beghelli S, et al (2009). Expression pattern of claudins 5 and 7 distinguishes solidpseudopapillaryfrom pancreatoblastoma, acinar cell and endocrinetumors of the pancreas. Am J Surg Pathol, 33, 768-74. https://doi.org/10.1097/PAS.0b013e3181957bc4
  7. Dehghan Esmatabadi MJ, Farhangi B, Safari Z, et al (2015). Dendrosomal curcumin inhibits metastatic potential of human SW480 colon cancer cells through down-regulation of Claudin1, Zeb1 and Hef1-1 gene expression. Asian Pac J Cancer Prev, 16, 2473-81. https://doi.org/10.7314/APJCP.2015.16.6.2473
  8. Eskelinen MJ, Haglund UH (1999). Prognosis of human pancreaticadenocarcinoma: review of clinical and histopathological variablesand possible uses of new molecular methods. Eur J Surg, 165, 292-306. https://doi.org/10.1080/110241599750006811
  9. Fritzsche FR, Oelrich B, Johannsen M, et al (2008). Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas. Clin Cancer Res, 14, 7035-42. https://doi.org/10.1158/1078-0432.CCR-08-0855
  10. Hsueh C, Chang YS, Tseng NM, et al (2010). Expression pattern and prognostic significance of claudins 1, 4, and 7 innasopharyngeal carcinoma. Hum Pathol, 41, 944-50 https://doi.org/10.1016/j.humpath.2010.01.005
  11. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  12. Karanjawala ZE, Illei PB, Ashfaq R, et al (2008). New markers of pancreatic cancer identified through differentialgene expression analyses: claudin 18 and annexin A8. Am JSurg Pathol, 32, 188-96. https://doi.org/10.1097/PAS.0b013e31815701f3
  13. Kojima T, Takano K, Yamamoto T, et al (2008). Transforming growth factor-beta induces epithelial to mesenchymal transition by down-regulation of claudin-1 expression and the fence function in adult rat hepatocytes. Liver Int, 28, 534-45.
  14. Kojima T, Sawada N (2012). Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells. Ann N Y Acad Sci, 1257, 85-92. https://doi.org/10.1111/j.1749-6632.2012.06579.x
  15. Kojima T, Kyuno D, Sawada N (2012). Targeting claudin-4 in human pancreatic cancer. Expert Opin Ther Targets, 16, 881-7. https://doi.org/10.1517/14728222.2012.708340
  16. Kominsky SL, Argani P, Korz D, et al (2003). 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, 2021-33. https://doi.org/10.1038/sj.onc.1206199
  17. Kondo J, Sato F, Kusumi T, et al (2008). Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells. Int J Mol Med, 22, 645-9.
  18. Konecny GE, Agarwal R, Keeney GA, et al (2008). Claudin-3 and Claudin-4 expression in serous papillary, clear cell, and endometrioid endometrial cancer. Gynecol Oncol, 109, 263-9. https://doi.org/10.1016/j.ygyno.2008.01.024
  19. Krause G, Winkler L, Mueller SL, et al (2008). Structure and function of Claudins. Biochim Biophys Acta, 1778, 631-45. https://doi.org/10.1016/j.bbamem.2007.10.018
  20. Kwon MJ, Kim SS, Choi YL, et al (2010). Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated withloss of repressive histone modifications. Carcinogenesis, 31, 974-983. https://doi.org/10.1093/carcin/bgp336
  21. Kwon MJ, Kim SH, Jeong HM, et al (2011). Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma. Lab Invest, 91, 1652-67. https://doi.org/10.1038/labinvest.2011.117
  22. Kyuno D, Kojima T, Yamaguchi H, et al (2013). Protein kinase $C{\alpha}$ inhibitor protects against downregulation of claudin-1 during epithelial-mesenchymal transition of pancreatic cancer. Carcinogenesis, 34, 1232-43. https://doi.org/10.1093/carcin/bgt057
  23. Landers KA, Samaratunga H, Teng L, et al (2008). Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer. Br J Cancer, 99, 491-501. https://doi.org/10.1038/sj.bjc.6604486
  24. Lechpammer M, Resnick MB, Sabo E, et al (2008). The diagnostic and prognostic utility of claudin expression in renal cell neoplasms. Mod Pathol. 21, 1320-9. https://doi.org/10.1038/modpathol.2008.116
  25. Michl P, Barth C, Buchholz M, et al (2003). Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res, 63, 6265-71.
  26. Neesse A, Griesmann H, Gress TM, Michl P (2012). Claudin-4 as therapeutic target in cancer. Arch Biochem Biophys, 524, 64-70. https://doi.org/10.1016/j.abb.2012.01.009
  27. Neesse A, Hahnenkamp A, Griesmann H, et al (2013). Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. Gut, 62, 1034-43. https://doi.org/10.1136/gutjnl-2012-302577
  28. Nichols LS, Ashfaq R, Iacobuzio-Donahue CA (2004). Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target. Am J Clin Pathol, 121, 226-30. https://doi.org/10.1309/K144PHVDDUPDD401
  29. Oliveira SS, Morgado-Diaz JA (2007). Claudins: multifunctional players in epithelial tight junctions and their role in cancer. Cell Mol Life Sci, 64, 17-28. https://doi.org/10.1007/s00018-006-6314-1
  30. Ouban A, Ahmed AA (2010). Claudins in human cancer: a review. Histol Histopathol, 25, 83-90.
  31. Pan XY, Wang B, Che YC, et al (2007). Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue. Int J Gynecol Cancer, 17, 233-241. https://doi.org/10.1111/j.1525-1438.2006.00748.x
  32. Rahner C, Mitic L, Anderson JM (2001). Heterogenity in expression and subcellu¬lar localization of Claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology, 120, 411-22. https://doi.org/10.1053/gast.2001.21736
  33. Rangel LB, Agarwal R, D'Souza T, et al (2003). Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. Clin Cancer Res, 9, 2567-75.
  34. Sheehan GM, Kallakury BV, Sheehan CE, et al (2007). Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas. Hum Pathol, 38, 564-9. https://doi.org/10.1016/j.humpath.2006.11.007
  35. Singh AB, Sharma A, Dhawan P(2010). Claudin family of proteins and cancer: an overview. J Oncol, 2010, 541957.
  36. Soini Y, Takasawa A, Eskelinen M, et al (2012). Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma: association with features of differentiation. J Clin Pathol, 65, 431-6. https://doi.org/10.1136/jclinpath-2011-200400
  37. Szekely E, Torzsok P, Riesz P, et al (2011). Expression of claudins and their prognostic significance in noninvasive urothelial neoplasms of the human urinary bladder. J Histochem Cytochem, 59, 932-41. https://doi.org/10.1369/0022155411418829
  38. Tan C, Cruet-Hennequart S, Troussard A, et al (2004). Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell, 5, 79-90. https://doi.org/10.1016/S1535-6108(03)00281-2
  39. Tsukahara M, Nagai H, Kamiakito T, et al (2005). Distinct expression patterns of claudin-1 and claudin-4 in intraductal papillary-mucinous tumors of the pancreas. Pathol Int, 55, 63-9. https://doi.org/10.1111/j.1440-1827.2005.01793.x
  40. Tsukita S, Furuse M, Itoh M (2001). Multifunctional strands in tight junctions. Nature Reviews Molecular Cell Biology, 2, 285-93. https://doi.org/10.1038/35067088
  41. Tsutsumi K, Sato N, Tanabe R, et al (2012). Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma. Ann Surg Oncol, 3, 491-9.
  42. Usami Y, Chiba H, Nakayama F, et al (2006). Reduced expression of Claudin-7 cor-relates with invasion and metastasis in squamous cell carcinoma of the esophagus. Human Pathology, 37, 569-77. https://doi.org/10.1016/j.humpath.2005.12.018
  43. Wang WJ, Qin SH, Zhang JW, et al (2014). Combination doxorubicin and interferon-α therapy stimulates immunogenicity of murine pancreatic cancer Panc02 cells via up-regulation of NKG2D ligands and MHC class I. Asian Pac J Cancer Prev, 15, 9667-72. https://doi.org/10.7314/APJCP.2014.15.22.9667
  44. Westmoreland JJ, Drosos Y, Kelly J et al. (2012).Dynamic distribution of claudin proteins in pancreatic epithelia undergoing morphogenesis or neoplastic transformation. Dev Dyn, 241, 583-94. https://doi.org/10.1002/dvdy.23740
  45. Will C, Fromm M, Muller D (2008). Claudin tight junction proteins: novel aspects in paracellular transport. Perit Dial Int, 28, 577-84.
  46. Yeo TP, Hruban RH, Leach SD, et al (2002). Pancreatic cancer. Curr Probl Cancer, 26, 176-275. https://doi.org/10.1067/mcn.2002.129579
  47. Yoon CH, Kim MJ, Park MJ, et al (2010). Claudin-1 acts through c-Abl-protein kinase Cdelta (PKCdelta) signaling and has a causal role in the acquisition of invasive capacity in human liver cells. J Biol Chem, 285, 226-33. https://doi.org/10.1074/jbc.M109.054189

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