Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Golgi Phosphoprotein 2 Down-regulates the Th1 Response in Human Gastric Cancer Cells by Suppressing IL-12A

  • Tang, Qing-Feng (Department of Clinical Laboratories & Experimental Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Ji, Qing (Department of Clinical Laboratories & Experimental Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Tang, Yu (Department of nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Hu, Song-Jiao (Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Bao, Yi-Jie (Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Peng, Wen (Department of nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Yin, Pei-Hao (Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine)
  • Published : 2013.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Golgi phosphoprotein 2 (GOLPH2) is a very important biomarker in a variety of diseases. Its biological function is not clear, particularly in gastric cancer. To investigate the role of GOLPH2 in human gastric cancer, and determine its effect on the Th1 lymphocyte response, its expression and that of IL-12A were measured by real-time PCR and immunohistochemistry. The relationship between GOLPH2 and IL-12A was analysed statistically. The effect of GOLPH2 on the Th1 lymphocyte response was investigated with an in vitro co-culture system. The results showed that in human gastric cancer, the expression of GOLPH2 was significantly higher and the expression of IL-12A was lower than in normal gastric mucosal tissues, and the expression levels of GOLPH2 and IL-12A were negatively correlated. In addition, obvious down-regulation of the Th1 response was observed when lymphocytes were co-cultured with gastric cancer SGC7901 cells over-expressing GOLPH2. GOLPH2 down-regulated the expression of IL-12A, and inhibited the expression of TNF-${\alpha}$ and IFN-${\gamma}$. The results indicated that GOLPH2 down-regulates the Th1 response via suppression of IL-12A in human gastric cancer, and this might provide a target for the prevention and treatment.

Keywords

References

  1. Airoldi I, Guglielmino R, Carra G, et al (2002). The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes. Haematologica, 87, 434-42.
  2. Boes M, Prodeus AP, Schmidt T, et al (1998). A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med, 188, 2381-6. https://doi.org/10.1084/jem.188.12.2381
  3. Clark IA (2007). How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Rev, 18, 335-43. https://doi.org/10.1016/j.cytogfr.2007.04.002
  4. Correa P (2013). Gastric cancer: overview. Gastroenterol Clin North Am, 42, 211-7. https://doi.org/10.1016/j.gtc.2013.01.002
  5. Fritzsche FR, Kristiansen G, Riener MO, et al (2010). GOLPH2 expression may serve as diagnostic marker in seminomas. BMC Urol, 10, 4. https://doi.org/10.1186/1471-2490-10-4
  6. Fritzsche FR, Riener MO, Dietel M, et al (2008). GOLPH2 expression in renal cell cancer. BMC Urol, 8, 15. https://doi.org/10.1186/1471-2490-8-15
  7. Gong Y, Long Q, Xie H, et al (2012). Cloning and characterization of human Golgi phosphoprotein 2 gene (GOLPH2/GP73/GOLM1) promoter. Biochem Biophys Res Commun, 421, 713-20. https://doi.org/10.1016/j.bbrc.2012.04.067
  8. Gray PW, Goeddel DV (1982). Structure of the human immune interferon gene. Nature, 298, 859-63. https://doi.org/10.1038/298859a0
  9. Hu L, Li L, Xie H, et al (2011).The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences. PLoS One, 6, e28207. https://doi.org/10.1371/journal.pone.0028207
  10. Kim HJ, Lv D, Zhang Y, et al (2012). Golgi phosphoprotein 2 in physiology and in diseases. Cell Biosci, 2, 31. https://doi.org/10.1186/2045-3701-2-31
  11. Kim JJ (2013). Upper gastrointestinal cancer and reflux disease. J Gastric Cancer, 13, 79-85. https://doi.org/10.5230/jgc.2013.13.2.79
  12. Kristiansen G, Fritzsche FR, Wassermann K, et al (2008). GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics. Br J Cancer, 99, 939-48. https://doi.org/10.1038/sj.bjc.6604614
  13. Laxman B, Morris DS, Yu J, et al (2008). A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res, 68, 645-9. https://doi.org/10.1158/0008-5472.CAN-07-3224
  14. Old LJ (1985). Tumor necrosis factor (TNF). Science, 230, 630-2. https://doi.org/10.1126/science.2413547
  15. Peluso I, Pallone F, Monteleone G (2006). Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance and therapeutic implication. World J Gastroenterol, 12, 5606-10.
  16. Pietrantonio F, De Braud F, Da Prat V, et al (2013). A review on biomarkers for prediction of treatment outcome in gastric cancer. Anticancer Res, 33, 1257-66.
  17. Reid RR, Prodeus AP, Khan W, et al (1997). Endotoxin shock in antibody-deficient mice: unraveling the role of natural antibody and complement in the clearance of lipopolysaccharide. J Immunol, 159, 970-5.
  18. Riener MO, Stenner F, Liewen H, et al (2009). Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology, 49, 1602-9. https://doi.org/10.1002/hep.22843
  19. Rival YA. Maschio D, Rabiet MJ, et al (1996). Inhibition of platelet endothelial cell adhesion molecule-1 synthesis and leukocyte transmigration in endothelial cells by the combined action of TNF-${\alpha}$ and IFN-${\gamma}$. J Immunol, 157, 1233.
  20. Romer LH, McLean NV, Yan HC, et al (1995). IFN-${\gamma}$ and TNF-${\alpha}induce$ redistribution of PECAM-1 (CD31) on human endothelial cells. J Immunol, 154, 6582.
  21. Roobol MJ, Haese A, Bjartell A (2011).Tumour markers in prostate cancer III: biomarkers in urine. Acta Oncol, 50 (Suppl 1), 85-9. https://doi.org/10.3109/0284186X.2010.524935
  22. Said EA, Dupuy FP, Trautmann L, et al (2010). Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nature Med, 16, 452-9. https://doi.org/10.1038/nm.2106
  23. Schoenborn JR, Wilson CB (2007). Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol, 96, 41-101. https://doi.org/10.1016/S0065-2776(07)96002-2
  24. Schroder K, Hertzog PJ, Ravasi T, et al (2004). Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 75, 163-89.
  25. Sugano K (2013). Premalignant conditions of gastric cancer. J Gastroenterol Hepatol, 28, 906-11. https://doi.org/10.1111/jgh.12209
  26. Wajant H, Pfizenmaier K, Scheurich P (2003). Tumor necrosis factor signaling. Cell Death Differ, 10, 45-65. https://doi.org/10.1038/sj.cdd.4401189
  27. Wang L, Zhao YH, Liu Y, et al (2013). IFN-${\gamma}$ and TNF-${\alpha}$ synergistically induce mesenchymal stem cell impairment and tumorigenesis via $NF{\kappa}B$ signaling. Stem Cells, 31, 1383-95. https://doi.org/10.1002/stem.1388
  28. Wei S, Dunn TA, Isaacs WB, et al (2008). GOLPH2 and MYO6: putative prostate cancer markers localized to the Golgi apparatus. Prostate, 68, 1387-95. https://doi.org/10.1002/pros.20806
  29. Wolf SF, Temple PA, Kobayashi M, et al (1991). Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol, 146, 3074-81.
  30. Zhang F, Gu Y, Li X, et al (2010). Up-regulated Golgi phosphoprotein 2 (GOLPH2) expression in lung adenocarcinoma tissue. Clin Biochem, 43, 983-91. https://doi.org/10.1016/j.clinbiochem.2010.05.010

Cited by

  1. Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance vol.17, pp.10, 2016, https://doi.org/10.3390/ijms17101619