Abstract
To investigate vasoactive intestinal peptide (VIP) effect on dendritic cells (DCs) to gastric cancer (GC) cells in vitro involving immune escape mechanism of GC, we observed DC-SIGN (CD209), Ii chain (CD74), MHC-II and collaborative costimulatory molecules CD40, CD80, CD86 expressions in DCs, which co-incubated with GC cells and VIP. Human umbilical cord blood (HUCB) were obtained from healthy volunteers and human mononuclear cells were isolated from HUCB by density gradient centrifugation. Monocytes were purified from mononuclear cells using adherence separation and were treated with recombinant human granulocyte–macrophage colony-stimulating factor (rh GM-CSF), recombinant human interleukin-4 (rh IL-4) to induce immature monocyte-derived DCs (moDCs). Recombinant human tumor necrosis factor (rh TNF-α) was added on the 5th day to induce mature moDCs. Mature moDCs were collected on the 10th day, and co-incubated with MKN45, VIP and mannan, respectively. CD1a and CD83 expressions were detected by immunocytochemistry. VIP, VPAC1, CD209, CD74, MHC-II, CD40, CD80 and CD86 expressions of DCs were detected by immunocytochemistry and RT-PCR. VPAC1 was detected in DCs, but VIP did not detected in DCs. When DCs were co-incubated with MKN45 cells, MKN45 cells could inhibit DCs’ expressions of CD209, CD74, MHC-II, CD40, CD80 and CD86 in the mRNA and protein levels (p < 0.05), and VIP could further inhibit CD209, CD74, MHC-II, CD40, CD80 and CD86 expressions of DCs in the mRNA and protein levels (p < 0.05). The inhibition could not been reversed by mannan. CD209 was positively correlated with CD74, MHC-II, CD40, CD80 and CD86 in mRNA level and protein expression intensity in DCs. VIP could inhibit CD209, CD74, MHC-II, CD40, CD80 and CD86 expressions of DCs, and inhibit antigen-presenting ability of DCs. VIP may promote immune escape of GC by inhibiting CD209, CD74, MHC-II, CD40, CD80 and CD86 expressions of DCs.
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References
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252. doi:10.1038/32588
Beswick EJ, Reyes VE (2009) CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. World J Gastroenterol 15:2855–2861
Binsky I et al (2007) IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival. Proc Natl Acad Sci USA 104:13408–13413. doi:10.1073/pnas.0701553104
Borghese F, Clanchy FI (2011) CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease. Expert Opin Ther Targets 15:237–251. doi:10.1517/14728222.2011.550879
Compare D, Rocco A, Nardone G (2010) Risk factors in gastric cancer. Eur Rev Med Pharmacol Sci 14:302–308
Datta MW, Shahsafaei A, Nadler LM, Freeman GJ, Dorfman DM (2000) Expression of MHC class II-associated invariant chain (Ii;CD74) in thymic epithelial neoplasms. Appl Immunohistochem Mol Morphol 8:210–215
Delgado M, Ganea D (2013) Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids 45:25–39. doi:10.1007/s00726-011-1184-8
Deng B et al (2013) Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-beta1 in gastric cancer. PLoS One 8:e63777. doi:10.1371/journal.pone.0063777
Diebold SS (2009) Activation of dendritic cells by toll-like receptors and C-type lectins. Handbook of experimental pharmacology. doi:10.1007/978-3-540-71029-5_1, pp 3–30
Engering A, Van Vliet SJ, Geijtenbeek TB, Van Kooyk Y (2002) Subset of DC-SIGN(+) dendritic cells in human blood transmits HIV-1 to T lymphocytes. Blood 100:1780–1786. doi:10.1182/blood-2001-12-0179
Fernandez-Martinez AB, Carmena MJ, Bajo AM, Vacas E, Sanchez-Chapado M, Prieto JC (2015) VIP induces NF-kappaB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells. Cell Signal 27:236–244. doi:10.1016/j.cellsig.2014.11.005
Ganea D, Delgado M (2001) Neuropeptides as modulators of macrophage functions. Regulation of cytokine production and antigen presentation by VIP and PACAP. Arch Immunol Ther Exp 49:101–110
Ganea D, Rodriguez R, Delgado M (2003) Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: players in innate and adaptive immunity. Cell Mol Biol 49:127–142
Ganea D, Hooper KM, Kong W (2015) The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol 213:442–452. doi:10.1111/apha.12427
Geijtenbeek TB, van Kooyk Y (2003) Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity. Acta Pathol Microbiol Immunol Scand 111:698–714
Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG (2000) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575–585
Groneberg DA, Rabe KF, Wagner U, Fischer A (2004) Vasoactive intestinal polypeptide in the respiratory tract: physiology and pathophysiology. Pneumologie 58:330–338. doi:10.1055/s-2004-818352
Guo P, Huang ZL, Yu P, Li K (2012) Trends in cancer mortality in China: an update. Ann Oncol 23:2755–2762. doi:10.1093/annonc/mds069
Gustafson WC, De Berry BB, Evers BM, Chung DH (2005) Role of gastrointestinal hormones in neuroblastoma. World J Surg 29:281–286. doi:10.1007/s00268-004-7815-4
Harmar AJ et al (2012) Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166:4–17. doi:10.1111/j.1476-5381.2012.01871.x
Hejna M et al (2001) Serum levels of vasoactive intestinal peptide (VIP) in patients with adenocarcinomas of the gastrointestinal tract. Anticancer Res 21:1183–1187
Iishi H, Tatsuta M, Baba M, Okuda S, Taniguchi H (1992) Enhancement by vaso-active intestinal peptide of gastric carcinogenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine in rats. Int J Cancer 50:649–652
Ishigami S et al (2001) Invariant chain expression in gastric cancer. Cancer Lett 168:87–91
Ishigami S et al (2003) Tumor-associated macrophage (TAM) infiltration in gastric cancer. Anticancer Res 23:4079–4083
Jiang Z, Xu M, Savas L, LeClair P, Banner BF (1999) Invariant chain expression in colon neoplasms. Virchows Archiv 435:32–36
Kim SW, Beauchamp RD, Townsend CM Jr, Thompson JC (1991) Vasoactive intestinal polypeptide inhibits c-myc expression and growth of human gastric carcinoma cells. Surgery 110:270–275
Langer I, Robberecht P (2007) Molecular mechanisms involved in vasoactive intestinal peptide receptor activation and regulation: current knowledge, similarities to and differences from the A family of G-protein-coupled receptors. Biochem Soc Trans 35:724–728. doi:10.1042/BST0350724
Li GH, Qian W, Song GQ, Hou XH (2007) Effect of vasoactive intestinal peptide on gastric adenocarcinoma. J Gastroenterol Hepatol 22:1328–1335. doi:10.1111/j.1440-1746.2007.04947.x
Liu S, Zeng Y, Li Y, Guo W, Liu J, Ouyang N (2014) VPAC1 overexpression is associated with poor differentiation in colon cancer. Tumour Biol 35:6397–6404. doi:10.1007/s13277-014-1852-x
Maldonado RA, von Andrian UH (2010) How tolerogenic dendritic cells induce regulatory T cells. Adv Immunol 108:111–165. doi:10.1016/B978-0-12-380995-7.00004-5
McClelland M, Zhao L, Carskadon S, Arenberg D (2009) Expression of CD74, the receptor for macrophage migration inhibitory factor, in non-small cell lung cancer. Am J Pathol 174:638–646. doi:10.2353/ajpath.2009.080463
Moody TW, Gozes I (2007) Vasoactive intestinal peptide receptors: a molecular target in breast and lung cancer. Curr Pharm Des 13:1099–1104
Nagata S et al (2009) CD74 is a novel prognostic factor for patients with pancreatic cancer receiving multimodal therapy. Ann Surg Oncol 16:2531–2538. doi:10.1245/s10434-009-0532-3
Peiser M, Wanner R, Kolde G (2004) Human epidermal Langerhans cells differ from monocyte-derived Langerhans cells in CD80 expression and in secretion of IL-12 after CD40 cross-linking. J Leukoc Biol 76:616–622. doi:10.1189/jlb.0703327
Quante M, Varga J, Wang TC, Greten FR (2013) The gastrointestinal tumor microenvironment. Gastroenterology 145:63–78. doi:10.1053/j.gastro.2013.03.052
Rappocciolo G et al (2006) DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. J Immunol 176:1741–1749
Relloso M et al (2002) DC-SIGN (CD209) expression is IL-4 dependent and is negatively regulated by IFN, TGF-beta, and anti-inflammatory agents. J Immunol 168:2634–2643
Reubi JC (2000) In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clin Implic Ann N Y Acad Sci 921:1–25
Reubi JC, Laderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA (2000) Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res 60:3105–3112
Roche PA, Furuta K (2015) The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 15:203–216. doi:10.1038/nri3818
Schulz S, Rocken C, Mawrin C, Weise W, Hollt V, Schulz S (2004) Immunocytochemical identification of VPAC1, VPAC2, and PAC1 receptors in normal and neoplastic human tissues with subtype-specific antibodies. Clin Cancer Res 10:8235–8242. doi:10.1158/1078-0432.CCR-04-0939
Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22. doi:10.1146/annurev-immunol-100311-102839
Takahashi A et al (2002) Correlation of vascular endothelial growth factor-C expression with tumor-infiltrating dendritic cells in gastric cancer. Oncology 62:121–127.
Takahashi T, Saikawa Y, Kitagawa Y (2013) Gastric cancer: current status of diagnosis and treatment. Cancers 5:48–63. doi:10.3390/cancers5010048
Tian B, Zhang Y, Li N, Liu X, Dong J (2012) CD74: a potential novel target for triple-negative breast cancer. Tumour Biol 33:2273–2277. doi:10.1007/s13277-012-0489-x
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012 CA. Cancer J Clin 65:87–108. doi:10.3322/caac.21262
Tu S et al (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:408–419. doi:10.1016/j.ccr.2008.10.011
Vaudry D et al (2009) Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 61:283–357. doi:10.1124/pr.109.001370
Wang RF (2009) Molecular cloning and characterization of MHC class I- and II-restricted tumor antigens recognized by T cells Current protocols in immunology/edited by John E Coligan et al Chapter 20:Unit 20 10 doi:10.1002/0471142735.im2010s84
Wang C, Zhou XJ, Li YY, Wan J, Yang LY, Li GH (2013) Effect of vasoactive intestinal peptide (VIP) on NKG2D signal pathway and its contribution to immune escape of MKN45 cells. Sci World J 2013:429545. doi:10.1155/2013/429545
Yoong J, Michael M, Leong T (2011) Targeted therapies for gastric cancer: current status. Drugs 71:1367–1384. doi:10.2165/11592530-000000000-00000
Zheng YX et al (2012) CD74 and macrophage migration inhibitory factor as therapeutic targets in gastric cancer. World J Gastroenterol 18:2253–2261. doi:10.3748/wjg.v18.i18.2253
Acknowledgments
This study was supported by the Nation Nature Science Fund of China (Grant No. 30960429) and the First Affiliated Hospital of Nanchang University.
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Xi-Jin Zhou and Feng-Li Wu contributed equally to this study and share first authorship.
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Xi-Jin Zhou, Feng-li Wu, Li-Li Jiang, Li-Fang Huang and Guo-Hua Li declare that they have no conflict of interest.
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The article does not contain studies with human or animal subjects that has been approved by the Review Board of The First Affiliated Hospital of Nanchang University.
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The common first author is Feng-li Wu.
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Zhou, XJ., Wu, Fl., Jiang, LL. et al. Vasoactive Intestinal Peptide Promotes Immune Escape of MKN45 Cells by Inhibiting Antigen-Presenting Molecules of Dendritic Cells In Vitro. Int J Pept Res Ther 22, 341–353 (2016). https://doi.org/10.1007/s10989-016-9513-0
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DOI: https://doi.org/10.1007/s10989-016-9513-0