Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response

Bu,Xuefeng; Li,Mi; Zhao,Yinghai; Liu,Sha; Wang,Mubin; Ge,Jinying; Bu,Zhigao; Yan,Yulan

doi:10.3892/or.2016.4925

Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response

Authors:
- Xuefeng Bu
- Mi Li
- Yinghai Zhao
- Sha Liu
- Mubin Wang
- Jinying Ge
- Zhigao Bu
- Yulan Yan
View Affiliations

Affiliations: Department of General Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Clinical Medicine College of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150001, P.R. China, Department of Internal Medicine, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China
Published online on: July 11, 2016 https://doi.org/10.3892/or.2016.4925
Pages: 1393-1402

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Interferon-λ1 (IFN-λ1), a recently discovered cytokine of the type III IFN family, was found to be a therapeutic alternative to type I IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN‑λ1 recombinant adenovirus (rL-hIFN-λ1) containing human IFN-λ1 gene and further evaluated the expressing of IFN-λ1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-λ1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-λl specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs.The expression of the IFN-λ1 proteins reached a high level detected in the supernatant harvested 24 h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-λ1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-λ1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and Annexin V flow cytometry. Due to the high dose of IFN-λ1 expressed by the rL-hIFN-λ1-infected tumor cells, the immune study showed that rL-hIFN-λ1 increased IFN-γ production [the T helper cell subtype 1 (Th1) response] and inhibited interleukin (IL)-13 production [the T helper cell subtype 2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-λ1 as an efficient antitumor agent.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Khalighinejad N, Hariri H, Behnamfar O, Yousefi A and Momeni A: Adenoviral gene therapy in gastric cancer: A review. World J Gastroenterol. 14:180–184. 2008. View Article : Google Scholar : PubMed/NCBI
3	Janke M, Peeters B, de Leeuw O, Moorman R, Arnold A, Fournier P and Schirrmacher V: Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther. 14:1639–1649. 2007. View Article : Google Scholar : PubMed/NCBI
4	Beutner U, Lorenz U, Illert B, Rott L, Timmermann W, Vollmers HP, Müller-Hermelink HK, Thiede A and Ulrichs K: Neoadjuvant therapy of gastric cancer with the human monoclonal IgM antibody SC-1: Impact on the immune system. Oncol Rep. 19:761–769. 2008.PubMed/NCBI
5	Krishnamurthy S and Samal SK: Nucleotide sequences of the trailer, nucleocapsid protein gene and intergenic regions of Newcastle disease virus strain Beaudette C and completion of the entire genome sequence. J Gen Virol. 79:2419–2424. 1998. View Article : Google Scholar : PubMed/NCBI
6	Bukreyev A and Collins PL: Newcastle disease virus as a vaccine vector for humans. Curr Opin Mol Ther. 10:46–55. 2008.PubMed/NCBI
7	Bukreyev A, Skiadopoulos MH, Murphy BR and Collins PL: Nonsegmented negative-strand viruses as vaccine vectors. J Virol. 80:10293–10306. 2006. View Article : Google Scholar : PubMed/NCBI
8	Ge J, Deng G, Wen Z, Tian G, Wang Y, Shi J, Wang X, Li Y, Hu S, Jiang Y, et al: Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. J Virol. 81:150–158. 2007. View Article : Google Scholar :
9	Ge J, Tian G, Zeng X, Jiang Y, Chen H and Bua Z: Generation and evaluation of a Newcastle disease virus-based H9 avian influenza live vaccine. Avian Dis. 54(Suppl 1): 294–296. 2010. View Article : Google Scholar : PubMed/NCBI
10	Elliott S, Egrie J, Browne J, Lorenzini T, Busse L, Rogers N and Ponting I: Control of rHuEPO biological activity: The role of carbohydrate. Exp Hematol. 32:1146–1155. 2004. View Article : Google Scholar : PubMed/NCBI
11	Sinclair AM and Elliott S: Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins. J Pharm Sci. 94:1626–1635. 2005. View Article : Google Scholar : PubMed/NCBI
12	Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, et al: IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 4:63–68. 2003. View Article : Google Scholar
13	Sommereyns C, Paul S, Staeheli P and Michiels T: IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog. 4:e10000172008. View Article : Google Scholar : PubMed/NCBI
14	Haabeth OA, Lorvik KB, Hammarström C, Donaldson IM, Haraldsen G, Bogen B and Corthay A: Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun. 2:2402011. View Article : Google Scholar : PubMed/NCBI
15	Mohty AM, Grob JJ, Mohty M, Richard MA, Olive D and Gaugler B: Induction of IP-10/CXCL10 secretion as an immunomodulatory effect of low-dose adjuvant interferon-alpha during treatment of melanoma. Immunobiology. 215:113–123. 2010. View Article : Google Scholar
16	Pertl U, Luster AD, Varki NM, Homann D, Gaedicke G, Reisfeld RA and Lode HN: IFN-gamma-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy. J Immunol. 166:6944–6951. 2001. View Article : Google Scholar : PubMed/NCBI
17	Tominaga M, Iwashita Y, Ohta M, Shibata K, Ishio T, Ohmori N, Goto T, Sato S and Kitano S: Antitumor effects of the MIG and IP-10 genes transferred with poly [D,L-2,4-diaminobutyric acid] on murine neuroblastoma. Cancer Gene Ther. 14:696–705. 2007. View Article : Google Scholar : PubMed/NCBI
18	Wang P, Yang X, Xu W, Li K, Chu Y and Xiong S: Integrating individual functional moieties of CXCL10 and CXCL11 into a novel chimeric chemokine leads to synergistic antitumor effects: A strategy for chemokine-based multi-target-directed cancer therapy. Cancer Immunol Immunother. 59:1715–1726. 2010. View Article : Google Scholar : PubMed/NCBI
19	Egeter O, Mocikat R, Ghoreschi K, Dieckmann A and Röcken M: Eradication of disseminated lymphomas with CpG-DNA activated T helper type 1 cells from nontransgenic mice. Cancer Res. 60:1515–1520. 2000.PubMed/NCBI
20	Müller-Hermelink N, Braumüller H, Pichler B, Wieder T, Mailhammer R, Schaak K, Ghoreschi K, Yazdi A, Haubner R, Sander CA, et al: TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell. 13:507–518. 2008. View Article : Google Scholar : PubMed/NCBI
21	Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ and Schreiber RD: IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 410:1107–1111. 2001. View Article : Google Scholar : PubMed/NCBI
22	Dai J, Megjugorac NJ, Gallagher GE, Yu RY and Gallagher G: IFN-lambda1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells. Blood. 113:5829–5838. 2009. View Article : Google Scholar : PubMed/NCBI
23	Sargurupremraj M, Pukelsheim K, Hofer T and Wjst M: Intermediary quantitative traits - an alternative in the identification of disease genes in asthma? Genes Immun. 15:1–7. 2014. View Article : Google Scholar
24	Stiff A and Carson Iii W: Investigations of interferon-lambda for the treatment of cancer. J Innate Immun. 7:243–250. 2015. View Article : Google Scholar : PubMed/NCBI
25	Bu X, Wang M, Zhang J, Liu J, Jia L, Liang B and Yan Y: Recombinant adenovirus expressing hIFN-λ1 inhibits gastric adenocarcinoma cell line SGC-7901 proliferation. Oncol Lett. 11:287–292. 2016.PubMed/NCBI
26	Wyatt LS, Moss B and Rozenblatt S: Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. Virology. 210:202–205. 1995. View Article : Google Scholar : PubMed/NCBI
27	Burkart C, Arimoto K, Tang T, Cong X, Xiao N, Liu YC, Kotenko SV, Ellies LG and Zhang DE: Usp18 deficient mammary epithelial cells create an antitumour environment driven by hypersensitivity to IFN-λ and elevated secretion of Cxcl10. EMBO Mol Med. 5:967–982. 2013. View Article : Google Scholar : PubMed/NCBI
28	Reichard KW, Lorence RM, Cascino CJ, Peeples ME, Walter RJ, Fernando MB, Reyes HM and Greager JA: Newcastle disease virus selectively kills human tumor cells. J Surg Res. 52:448–453. 1992. View Article : Google Scholar : PubMed/NCBI
29	Foucault C, Mordant P, Grand B, Achour K, Arame A, Dujon A, Le Pimpec Barthes F and Riquet M: Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: Revisiting exploratory thoracotomies and incomplete resections. Interact Cardiovasc Thorac Surg. 16:667–672. 2013. View Article : Google Scholar : PubMed/NCBI
30	Vähä-Koskela MJ, Heikkilä JE and Hinkkanen AE: Oncolytic viruses in cancer therapy. Cancer Lett. 254:178–216. 2007. View Article : Google Scholar : PubMed/NCBI
31	Hossain A, Radwan FF, Doonan BP, God JM, Zhang L, Bell PD and Haque A: A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma. Apoptosis. 17:1066–1078. 2012. View Article : Google Scholar : PubMed/NCBI
32	Lam HY, Yeap SK, Rasoli M, Omar AR, Yusoff K, Suraini AA and Alitheen NB: Safety and clinical usage of Newcastle disease virus in cancer therapy. J Biomed Biotechnol. 2011:7187102011. View Article : Google Scholar : PubMed/NCBI
33	Nakaya T, Cros J, Park MS, Nakaya Y, Zheng H, Sagrera A, Villar E, García-Sastre A and Palese P: Recombinant Newcastle disease virus as a vaccine vector. J Virol. 75:11868–11873. 2001. View Article : Google Scholar : PubMed/NCBI
34	Lasfar A, Abushahba W, Balan M and Cohen-Solal KA: Interferon lambda: A new sword in cancer immunotherapy. Clin Dev Immunol. 2011:3495752011. View Article : Google Scholar : PubMed/NCBI
35	Steen HC and Gamero AM: Interferon-lambda as a potential therapeutic agent in cancer treatment. J Interferon Cytokine Res. 30:597–602. 2010. View Article : Google Scholar : PubMed/NCBI
36	Jordan WJ, Eskdale J, Srinivas S, Pekarek V, Kelner D, Rodia M and Gallagher G: Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response. Genes Immun. 8:254–261. 2007. View Article : Google Scholar : PubMed/NCBI
37	Ding S, Khoury-Hanold W, Iwasaki A and Robek MD: Epigenetic reprogramming of the type III interferon response potentiates antiviral activity and suppresses tumor growth. PLoS Biol. 12:e10017582014. View Article : Google Scholar : PubMed/NCBI
38	Elankumaran S, Rockemann D and Samal SK: Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J Virol. 80:7522–7534. 2006. View Article : Google Scholar : PubMed/NCBI
39	Hrabák A, Csuka I, Bajor T and Csatáry LK: The cytotoxic antitumor effect of MTH-68/H, a live attenuated Newcastle disease virus is mediated by the induction of nitric oxide synthesis in rat peritoneal macrophages in vitro. Cancer Lett. 231:279–289. 2006. View Article : Google Scholar
40	Bian H, Fournier P, Peeters B and Schirrmacher V: Tumor-targeted gene transfer in vivo via recombinant Newcastle disease virus modified by a bispecific fusion protein. Int J Oncol. 27:377–384. 2005.PubMed/NCBI
41	Lorence RM, Rood PA and Kelley KW: Newcastle disease virus as an antineoplastic agent: Induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity. J Natl Cancer Inst. 80:1305–1312. 1988. View Article : Google Scholar : PubMed/NCBI
42	Bu XF, Wang MB, Zhang ZJ, Zhao YH, Li M and Yan YL: Autophagy is involved in recombinant Newcastle disease virus (rL-RVG)-induced cell death of stomach adenocarcinoma cells in vitro. Int J Oncol. 47:679–689. 2015.PubMed/NCBI
43	Fábián Z, Töröcsik B, Kiss K, Csatary LK, Bodey B, Tigyi J, Csatary C and Szeberényi J: Induction of apoptosis by a Newcastle disease virus vaccine (MTH-68/H) in PC12 rat phaeochromo-cytoma cells. Anticancer Res. 21(1A): 125–135. 2001.PubMed/NCBI
44	Fábián Z, Csatary CM, Szeberényi J and Csatary LK: p53-independent endoplasmic reticulum stress-mediated cytotoxicity of a Newcastle disease virus strain in tumor cell lines. J Virol. 81:2817–2830. 2007. View Article : Google Scholar : PubMed/NCBI
45	Fábián Z, Vecsernyés M, Pap M and Szeberényi J: The effects of a mutant p53 protein on the proliferation and differentiation of PC12 rat phaeochromocytoma cells. J Cell Biochem. 99:1431–1441. 2006. View Article : Google Scholar : PubMed/NCBI