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Influence of sCD40L on gastric cancer cell lines

Abstract

The CD40 signaling pathway plays a key role in tumor cell proliferation, differentiation, and apoptosis. Gastric cancer usually possesses a higher level of CD40 expression than normal tissue. We evaluated inhibition of soluble CD40 ligand (sCD40L) in apoptosis induction of gastric cancer cells. Gastric cancer cells (AGS and BGC-823) were incubated with sCD40L. Cell viability and cell cycle were determined by methyl-tetrazolium (MTT) assay and flow cytometry, respectively. The results showed that sCD40L hindered cell growth, arrested cells at G0/G1 phase and induced apoptosis. In conclusion, sCD40L suppress growth of gastric cancer cells through apoptosis induction and cell cycle quiescence. This work will provided a new approach to gene therapy of gastric cancer.

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References

  1. Kizaki H, Ohnishi Y, Mizuno Y, Azuma Y, Mizuno Y, Ohsaka F (1992) Arabinolcytosine and 5′-azacytisine induce internucleosomal DNA fragmentation and cell death in thymocytes. Immunopharmacology 24:219–227

    PubMed  Article  CAS  Google Scholar 

  2. Askew DS, Ashmun RA, Simmons BC, Cleveland JL (1991) Constitutive c-myc expression in an IL-3 dependent myeloid ce ll line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922

    PubMed  CAS  Google Scholar 

  3. Mocali A, Cedrola S, Della Malva N, Bontempelli M, Mitidieri VAM, Bavazzano A, Comolli R, Paoletti F, La Porta CAM (2004) Increased plasma levels of soluble CD40, together with the decrease of TGFβ1, as possible differential markers of Alzheimer disease. Exp Gerontol 39:1555–1561

    PubMed  Article  CAS  Google Scholar 

  4. Calingasan NY, Erdely HA, Altar CA (2002) Identification of CD40 ligand in Alzheimer’s disease and in animal models of Alzheimer’s disease and brain injury. Neurobiol Aging 23:31–39

    PubMed  Article  CAS  Google Scholar 

  5. Futagami S, Hiratsuka T, Suzuki K, Tatsuguchi A, Kusunoki M, Shinji Y, Shinoki K, Gudis K, Nishigaki H, Wada K, Miyake K, Tsukui T, Sakamoto C (2003) COX-2 and VEGF expression in endothelial cells through their interaction with CD40-CD40 ligand in Helicobacter pylori infection. Gastroenterology 124:A403–A404

    Article  Google Scholar 

  6. Zhang L, Huang H, Wu K, Wang M, Wu B (2010) Impact of BTG2 expression on proliferation and invasion of gastric cancer cells in vitro. Mol Biol Rep 37(6):2579–2586

    PubMed  Article  CAS  Google Scholar 

  7. Hou R, Cao B, Chen Z, Li Y, Ning T, Li C, Xu C, Chen Z (2010) Association of cytotoxic T lymphocyte-associated antigen-4 gene haplotype with the susceptibility to gastric cancer. Mol Biol Rep 37(1):515–520

    PubMed  Article  CAS  Google Scholar 

  8. Ruybal P, José Gravisaco M, Barcala V, Escalada A, Di Sciullo P, Waldner C, Mongini C (2008) Complete rejection of a T-cell lymphoma due to synergism of T-cell receptor costimulatory molecules, CD80, CD40L, and CD40. Vaccine 26:697–705

    PubMed  Article  CAS  Google Scholar 

  9. Eeva J, Ropponen A, Nuutinen U, Eeva S-T, Mättö M, Eray M, Pelkonen J (2007) The CD40-induced protection against CD95-mediated apoptosis is associated with a rapid upregulation of anti-apoptotic c-FLIP. Mol Immunol 44:1230–1237

    PubMed  Article  CAS  Google Scholar 

  10. Shi L, Zhao M, Luo Q, Ma YM, Zhong JL, Yuan XH, Huang CZ (2010) Overexpression of PIP5KL1 suppresses cell proliferation and migration in human gastric cancer cells. Mol Biol Rep 37(5):2189–2198

    PubMed  Article  CAS  Google Scholar 

  11. Grewal IS, Flavell RA (1998) CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 16:111–135

    PubMed  Article  CAS  Google Scholar 

  12. Tong AW, Stone MJ (2003) Prospects for CD40-directed experimental therapy of human cancer. Cancer Gene Ther 10:1–13

    PubMed  Article  CAS  Google Scholar 

  13. Hirano A, Longo DL, Taub DD, Ferris DK, Young LS, Eliopoulos AG, Agathanggelou A, Cullen N, Macartney J, Fanslow WC (1999) Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. Blood 93:2999–3007

    PubMed  CAS  Google Scholar 

  14. Alexandroff AB, Jackson AM, Paterson T, Haley JL, Ross JA, Longo DL, Murphy WJ, James K, Taub DD (2000) Role for CD40-CD40 ligand interactions in the immune response to solid tumours. Mol Immunol 37:515–526

    PubMed  Article  CAS  Google Scholar 

  15. Xu J, Gao DF, Yan GL, Fan JM (2009) Induced apoptotic action of recombinant trichosanthin in human stomach adenocarcinoma MCG803 cells. Mol Biol Rep 36(6):1559–1564

    PubMed  Article  CAS  Google Scholar 

  16. Hodgkin PD, Yamashita LC, Seymour B, Coffman RL, Kehry MR (1991) Membranes from both Th1 and Th2 T-cell clones stimulate B cell proliferation and prepare B cells for lymphokine-induced differentiation to secrete Ig. J Immunol 147(11):3696–3702

    PubMed  CAS  Google Scholar 

  17. Grewal IS, Xu J, Flavell RA (1995) Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature 378(6557):617–620

    PubMed  Article  CAS  Google Scholar 

  18. DeKruyff RH, Gieni RS, Umetsu DT (1997) Antigen-driven but not lipopolysaccharide driven IL-12 production in macrophages requires triggering of CD40. J Immunol 158(1):359–366

    PubMed  CAS  Google Scholar 

  19. Koch F, Stanzl U, Jennewein P, Janke K, Heufler C, Kampgen E (1996) High level IL-12 production by murine dendritic cells: upregulation viaMHCclass II andCD40 molecules and downregulation by IL-4 and IL-10. J Exp Med 184(2):741–746

    PubMed  Article  CAS  Google Scholar 

  20. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G (1996) Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T-cell stimulatory capacity: T–T help via APC activation. J Exp Med 184(2):747–752

    PubMed  Article  CAS  Google Scholar 

  21. Wingett DG, Vestal RE, Forcier K, Hadjokas N (1998) Nielson CP: CD40 is functionally expressed on human breast carcinomas: variable inducibility by cytokines and enhancement of Fas-mediated apoptosis. Breast Cancer Res Treat 50:27–36

    PubMed  Article  CAS  Google Scholar 

  22. Pedersen AE, Thorn M, Gad M, Walter MR, Johnsen HE, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH, Svane IM (2005) Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination. Scand J Immunol 61:147–156

    PubMed  Article  CAS  Google Scholar 

  23. Pinzon-Charry A, Schmidt CW, López JA (2006) The key role of CD40 ligand in overcoming tumor-induced dendritic cell dysfunction. Breast Cancer Res 8:402

    PubMed  Article  Google Scholar 

  24. Masoudi M, Saadat I, Omidvari S, Saadat M (2009) Genetic polymorphisms of GSTO2, GSTM1, and GSTT1 and risk of gastric cancer. Mol Biol Rep 36(4):781–784

    PubMed  Article  CAS  Google Scholar 

  25. Li R, Chen W-C, Wang W-P, Tian W-Y, Zhang X-G (2009) Optimization of extraction technology of Astragalus polysaccharides by response surface methodology and its effect on CD40. Carbohydr Polym 78:784–788

    Article  CAS  Google Scholar 

  26. Li R, Chen W-C, Wang W-P, Tian W-Y, Zhang X-G (2009) Extraction, characterization of Astragalus polysaccharides and its immune modulating activities in rats with gastric cancer. Carbohydr Polym 78:738–742

    Article  CAS  Google Scholar 

  27. Li R, Chen W-C, Pang X-Q, Hua C, Li L, Zhang X-G (2009) Expression of CD40 and CD40L in gastric cancer tissue and its clinical significance. Int J Mol Sci 10:3900–3917

    PubMed  Article  CAS  Google Scholar 

  28. Li R, Chen W-C, Wang W-P, Tian W-Y, Zhang X-G (2010) CD40 signaling activated by agonistic anti-CD40 monoclonal antibody 5C11 has different effects on biological behavior of gastric carcinoma cells. Immunol Lett 131:120–125

    PubMed  Article  CAS  Google Scholar 

  29. Tolis C, Peters GJ, Ferreira CG, Pinedo HM, Giaccone G (1999) Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines. Eur J Cancer 35:796–807

    PubMed  Article  CAS  Google Scholar 

  30. Wang N, Dong XJ, Zhou RM, Guo W, Zhang XJ, Li Y (2009) An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China. Mol Biol Rep 36(2):357–364

    PubMed  Article  CAS  Google Scholar 

  31. Joo H-G, Fleming TP, Tanaka Y, Dunn TJ, Linehan DC, Goedegebuure PS, Eberlein TJ (2002) Human dendritic cells induce tumor-specific apoptosis by soluble factors. Int J Cancer 102:20–28

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

The work was supported by the National Natural Science Foundation of China (No. 30872943), the Natural Science Foundation of Jiangsu Province (BK2010231) and the social development projects of Suzhou (No. SS0711) and postgraduate innovative plan project of Jiangsu Province in 2009 (No: CX09B-033Z).

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Correspondence to Wei-Chang Chen.

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Li, R., Chen, WC., Pang, XQ. et al. Influence of sCD40L on gastric cancer cell lines. Mol Biol Rep 38, 5459 (2011). https://doi.org/10.1007/s11033-011-0702-9

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  • DOI: https://doi.org/10.1007/s11033-011-0702-9

Keywords

  • Apoptosis
  • sCD40L
  • Cell cycle
  • Gastric cancer
  • AGS
  • BGC-823