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Open Access 01-12-2022 | Glioblastoma | Research

The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant Newcastle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model

Authors: Sung Hoon Jang, Bo-Kyoung Jung, Yong Hee An, Hyun Jang

Published in: Virology Journal | Issue 1/2022

Abstract

Background

Glioblastoma is one of the most serious brain cancer. Previous studies have demonstrated that PTEN function disorder affects the causing and exacerbation of glioblastoma. Newcastle disease virus (NDV) has been studied as a cancer virotherapeutics. In this study, PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma.

Methods

We did comparison tests PTEN protein expression efficiency and oncolytic effect depend on the PTEN gene insertion site at the between NP and P genes and the between P and M gene. PTEN protein mRNA transcription, translation in glioblastoma cell, and functional PTEN protein effect of the rNDV in vitro and in vivo test performed using western blotting, RT-qPCR, MTT assay, and Glioblastoma xenograft animal model test.

Results

The result of this study demonstrates that rNDV-PTEN kills glioblastoma cells and reduces cancer tissue better than rNDV without the PTEN gene. In molecular immunological and cytological assays, PTEN expression level was high at located in the between NP and P gene, and PTEN gene was successfully delivered to the glioblastoma cell using rNDV and PTEN gene translated to functional protein and inhibits hTERT and AKT gene.

Conclusions

PTEN gene enhances the oncolytic effect of the rNDV. And our study demonstrated that NP and P gene site is better than P and M gene site which is commonly and conventionally used. PTEN gene containing rNDV is a good candidate virotherapeutics for glioblastoma.

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Lu M, Zhang X, Zhang M, Chen H, Dou W, Li S, Dai J. Non-model segmentation of brain glioma tissues with the combination of DWI and fMRI signals. Biomed Mater Eng. 2015;26:S1315–24.PubMed

Chow KK, Naik S, Kakarla S, Brawley VS, Shaffer DR, Yi Z, Rainusso N, Wu MF, Liu H, Kew Y, et al. T cells redirected to EphA2 for the immunotherapy of glioblastoma. Mol Ther. 2013;21:629–37. https://doi.org/10.1038/mt.2012.210.CrossRefPubMed

Englot DJ, Berger MS, Chang EF, Garcia PA. Characteristics and treatment of seizures in patients with high-grade glioma: a review. Neurosurg Clin N Am. 2012;23:227–35. https://doi.org/10.1016/j.nec.2012.01.009.CrossRefPubMed

Siu A, Wind JJ, Iorgulescu JB, Chan TA, Yamada Y, Sherman JH. Radiation necrosis following treatment of high grade glioma—a review of the literature and current understanding. Acta Neurochir (Wien). 2012;154:191–201. https://doi.org/10.1007/s00701-011-1228-6.CrossRef

Taphoorn MJ, Bottomley A. Health-related quality of life and symptom research in glioblastoma multiforme patients. Expert Rev Pharmacoecon Outcomes Res. 2005;5:763–74. https://doi.org/10.1586/14737167.5.6.763.CrossRefPubMed

Delgado-López PD, Corrales-Garcia EM. Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol. 2016;18:1062–71. https://doi.org/10.1007/s12094-016-1497-x.CrossRefPubMed

Benjamin R, Capparella J, Brown A. Classification of glioblastoma multiforme in adults by molecular genetics. Cancer J. 2003;9:82–90. https://doi.org/10.1097/00130404-200303000-00003.CrossRefPubMed

Ortega A, Sarmiento JM, Ly D, Nuño M, Mukherjee D, Black KL, Patil CG. Multiple resections and survival of recurrent glioblastoma patients in the temozolomide era. J Clin Neurosci. 2016;24:105–11. https://doi.org/10.1016/j.jocn.2015.05.047.CrossRefPubMed

Koekkoek JA, Postma TJ, Heimans JJ, Reijneveld JC, Taphoorn MJ. Antiepileptic drug treatment in the end-of-life phase of glioma patients: a feasibility study. Support Care Cancer. 2015;24:1633–8. https://doi.org/10.1007/s00520-015-2930-3.CrossRefPubMedPubMedCentral

10.

LaRocca CJ, Davydova J. Oncolytic virotherapy increases the detection of microscopic metastatic disease at time of staging laparoscopy for pancreatic adenocarcinoma. EBioMedicine. 2016;7:15–6. https://doi.org/10.1016/j.ebiom.2016.05.019.CrossRefPubMedPubMedCentral

11.

Cassel WA, Murray DR. A ten-year follow-up on stage II malignant melanoma patients treated postsurgically with Newcastle disease virus oncolysate. Med Oncol Tumor Pharmacother. 1992;9:169–71.CrossRef

12.

Yaacov B, Eliahoo E, Lazar I, Ben-Shlomo M, Greenbaum I, Panet A, Zakay-Rones Z. Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors. Cancer Gene Ther. 2008;15:795–807. https://doi.org/10.1038/cgt.2008.31.CrossRefPubMed

13.

Liang W, Wang H, Sun TM, Yao WQ, Chen LL, Jin Y, Li CL, Meng FJ. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive tract. World J Gastroenterol. 2003;9:495–8. https://doi.org/10.3748/wjg.v9.i3.495.CrossRefPubMedPubMedCentral

14.

Song KY, Wong J, Gonzalez L, Sheng G, Zamarin D, Fong Y. Antitumor efficacy of viral therapy using genetically engineered Newcastle disease virus [NDV(F3aa)-GFP] for peritoneally disseminated gastric cancer. J Mol Med (Berl). 2010;88:589–96. https://doi.org/10.1007/s00109-010-0605-6.CrossRef

15.

Puhlmann J, Puehler F, Mumberg D, Boukamp P, Beier R. Rac1 is required for oncolytic NDV replication in human cancer cells and establishes a link between tumorigenesis and sensitivity to oncolytic virus. Oncogene. 2010;29:2205–16. https://doi.org/10.1038/onc.2009.507.CrossRefPubMed

16.

Janke M, Peeters B, de Leeuw O, Moorman R, Arnold A, Fournier P, Schirrmacher V. Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther. 2007;14:1639–49. https://doi.org/10.1038/sj.gt.3303026.CrossRefPubMed

17.

Schirrmacher V. Fifty years of clinical application of newcastle disease virus: time to celebrate! Biomedicines. 2016;4(3):16. https://doi.org/10.3390/biomedicines4030016.CrossRefPubMedCentral

18.

Zamarin D, Palese P. Oncolytic Newcastle disease virus for cancer therapy: old challenges and new directions. Future Microbiol. 2012;7(3):347–67. https://doi.org/10.2217/fmb.12.4.CrossRefPubMed

19.

Fan X, Lu H, Cui Y, Hou X, Huang C, Liu G. Overexpression of p53 delivered using recombinant NDV induces apoptosis in glioma cells by regulating the apoptotic signaling pathway. Exp Ther Med. 2018;15(5):4522–30. https://doi.org/10.3892/etm.2018.5935.CrossRefPubMedPubMedCentral

20.

Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–8.CrossRef

21.

Parsons DW, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–12.CrossRef

22.

Perozo F, Villegas P, Dolz R, Afonso CL, Purvis LB. The VG/GA strain of Newcastle disease virus: mucosal immunity, protection against lethal challenge and molecular analysis. Avian Pathol. 2008;37(3):237–45. https://doi.org/10.1080/03079450802043734.CrossRefPubMed

23.

Davis LG, Dibner MD, Battey JF. SECTION 4–1—pBR322. In: Davis LG, Dibner MD, Battey JF, editors. Basic methods in molecular biology. Amsterdam: Elsevier; 1986. p. 24–5. https://doi.org/10.1016/B978-0-444-01082-7.50010-2.CrossRef

24.

Taylor SC, Berkelman T, Yadav G, Hammond M. A defined methodology for reliable quantification of Western blot data. Mol Biotechnol. 2013;55(3):217–26. https://doi.org/10.1007/s12033-013-9672-6.CrossRefPubMedPubMedCentral

25.

Yang Y, Shao N, Luo G, et al. Mutations of PTEN gene in gliomas correlate to tumor differentiation and short-term survival rate. Anticancer Res. 2010;30(3):981–5.PubMed

26.

Shin K-H, Park YJ, Park J-G. PTEN gene mutations in colorectal cancers displaying microsatellite instability. Cancer Lett. 2001;174(2):189–94.CrossRef

27.

Risinger JI, Hayes K, Maxwell GL, et al. PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res. 1998;4(12):3005–10.PubMed

28.

Zhang HY, Liang F, Jia ZL, Song ST, Jiang ZF. PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett. 2013;6(1):161–8. https://doi.org/10.3892/ol.2013.1331.CrossRefPubMedPubMedCentral

29.

Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB. PTEN Mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. JNCI: J Natl Cancer Inst. 2001;93(16):1246–56. https://doi.org/10.1093/jnci/93.16.1246.CrossRefPubMed

30.

Yang JM, Schiapparelli P, Nguyen HN, et al. Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization. Oncogene. 2017;36:3673–85. https://doi.org/10.1038/onc.2016.493.CrossRefPubMedPubMedCentral

31.

Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R. Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 1997;57(19):4183–6.PubMed

32.

Benitez JA, Ma J, D’antonio M, et al. PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3 [published correction appears in Nat Commun. 2018 May 25;9:16217]. Nat Commun. 2017;8:15223. https://doi.org/10.1038/ncomms15223.CrossRefPubMedPubMedCentral

33.

Yang JM, Schiapparelli P, Nguyen HN, et al. Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization. Oncogene. 2017;36(26):3673–85. https://doi.org/10.1038/onc.2016.493.CrossRefPubMedPubMedCentral

34.

Liu L, Huang L, He J, et al. PTEN inhibits non-small cell lung cancer cell growth by promoting G₀/G₁ arrest and cell apoptosis. Oncol Lett. 2019;17(1):1333–40. https://doi.org/10.3892/ol.2018.9719.CrossRefPubMed

35.

Thomas AA, Ernstoff MS, Fadul CE. Immunotherapy for the treatment of glioblastoma. Cancer J. 2012;18:59–68. https://doi.org/10.1097/PPO.0b013e3182431a73.CrossRefPubMedPubMedCentral

36.

Larsen CJ. Cellular immunotherapy and glioblastoma: a hopeful treatment? Bull Cancer. 2011;98:457.CrossRef

37.

Varghese S, Rabkin SD, Nielsen GP, MacGarvey U, Liu R, Martuza RL. Systemic therapy of spontaneous prostate cancer in transgenic mice with oncolytic herpes simplex viruses. Cancer Res. 2007;67:9371–9. https://doi.org/10.1158/0008-5472.CAN-07-0674.CrossRefPubMed

38.

Husain SR, Behari N, Kreitman RJ, Pastan I, Puri RK. Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res. 1998;58:3649–53.PubMed

39.

Debinski W, Gibo DM, Obiri NI, Kealiher A, Puri RK. Novel anti-brain tumor cytotoxins specific for cancer cells. Nat Biotechnol. 1998;16:449–53. https://doi.org/10.1038/nbt0598-449.CrossRefPubMed

40.

Bera TK, Viner J, Brinkmann E, Pastan I. Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2. Cancer Res. 1999;59:4018–22.PubMed

41.

Ghetie MA, Richardson J, Tucker T, Jones D, Uhr JW, Vitetta ES. Antitumor activity of Fab’ and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites. Cancer Res. 1991;51:5876–80.PubMed

42.

Altenburg AF, van Trierum SE, de Bruin E, et al. Effects of pre-existing orthopoxvirus-specific immunity on the performance of Modified Vaccinia virus Ankara-based influenza vaccines. Sci Rep. 2018;8:6474. https://doi.org/10.1038/s41598-018-24820-2.CrossRefPubMedPubMedCentral

43.

Tang Y, Han T, Everts M, Zhu ZB, Gillespie GY, Curiel DT, Wu H. Directing adenovirus across the blood-brain barrier via melanotransferrin (P97) transcytosis pathway in an in vitro model. Gene Ther. 2007;14(6):523–32. https://doi.org/10.1038/sj.gt.3302888.CrossRefPubMed

44.

Cuoco JA, Rogers CM, Mittal S. The oncolytic Newcastle disease virus as an effective immunotherapeutic strategy against glioblastoma. Neurosurg Focus FOC. 2021;50(2):E8.CrossRef

45.

Okwor E, Okoye JOA, Eze D. Studies on the time of detection of Newcastle disease virus in the brain in relation to other organs. J Anim Vet Adv. 2010. https://doi.org/10.3923/javaa.2010.946.948.CrossRef

46.

Vadlamudi S, Hanson RP. Invasion of the brain of chicken by Newcastle disease virus. Avian Dis. 1966;10(1):122–7. https://doi.org/10.2307/1588216.CrossRef

47.

Holman DH, Wang D, Woraratanadharm J, Dong JY. Chapter 7—viral vectors. In: Barrett ADT, Stanberry LR, editors. Vaccines for biodefense and emerging and neglected diseases. London: Academic Press; 2009. p. 77–91. https://doi.org/10.1016/B978-0-12-369408-9.00007-X.CrossRef

48.

Veits J, Wiesner D, Fuchs W, Hoffmann B, Granzow H, Starick E, Mundt E, Schirrmeier H, Mebatsion T, Mettenleiter TC, Römer-Oberdörfer A. Newcastle disease virus expressing H5 hemagglutinin gene protects chickens against Newcastle disease and avian influenza. Proc Natl Acad Sci U S A. 2006;103(21):8197–202. https://doi.org/10.1073/pnas.0602461103.CrossRefPubMedPubMedCentral

49.

Manoharan VK, Khattar SK, LaBranche CC, et al. Modified Newcastle Disease virus as an improved vaccine vector against Simian Immunodeficiency virus. Sci Rep. 2018;8:8952. https://doi.org/10.1038/s41598-018-27433-x.CrossRefPubMedPubMedCentral

50.

Nakaya T, Cros J, Park MS, Nakaya Y, Zheng H, Sagrera A, Villar E, García-Sastre A, Palese P. Recombinant Newcastle disease virus as a vaccine vector. J Virol. 2001;75(23):11868–73. https://doi.org/10.1128/JVI.75.23.11868-11873.2001.CrossRefPubMedPubMedCentral

51.

Schirrmacher V, Fournier P. Newcastle disease virus: a promising vector for viral therapy, immune therapy, and gene therapy of cancer. Methods Mol Biol. 2009;542:565–605. https://doi.org/10.1007/978-1-59745-561-9_30.CrossRefPubMed

52.

Kim SH, Samal SK. Newcastle disease virus as a vaccine vector for development of human and veterinary vaccines. Viruses. 2016;8(7):183. https://doi.org/10.3390/v8070183.CrossRefPubMedCentral

53.

Zhao W, Zhang Z, Zsak L, Yu Q. P and M gene junction is the optimal insertion site in Newcastle disease virus vaccine vector for foreign gene expression. J Gen Virol. 2015;96(Pt 1):40–5. https://doi.org/10.1099/vir.0.068437-0.CrossRefPubMed

Title: The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant Newcastle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model
Authors: Sung Hoon Jang
Bo-Kyoung Jung
Yong Hee An
Hyun Jang
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Published in: Virology Journal / Issue 1/2022
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-022-01746-w

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