Characteristics of Oncolytic Adenovirus Replication and Gene Expression in Hypoxic Condition

  • Kim, Hong-Sung (Department of Biomedical Laboratory Science, Korea Nazarene University)
  • Received : 2011.07.07
  • Accepted : 2011.09.27
  • Published : 2011.09.30

Abstract

Adenovirus type 5 (Ad5) vectors have been used for gene transfer to a wide variety of cell types in vivo and in vitro. The advantages of adenovirus vectors include the high titer of virus readily obtained in large scale preparations, their ability to transduce dividing and non dividing cells, and the high level of transgene expression. Since adenovirus vectors do not integrate in host cell DNA, there is a lack of insertional mutagenesis. However, many human tumor cells lack expression of the adenovirus 5 receptors and contain areas of hypoxia. In order to identify the pattern of replication and gene expression of oncolytic adenovirus in hypoxic condition, multiple different fiber modified Ads (Ad5F/S11, Ad5F/S35, Ad5F/K7, Ad5F/K21, and Ad5F/RGD) was compared. The replication of all fiber modified adenovirus was inhibited in hypoxic condition in HEK 293 cells, but gene expression has variety on different tumor cell lines and the level of coxackievirus and adenovirus receptor (CAR) expression. These data suggest that CAR expression pattern and hypoxic condition of tumor are considered for optimal oncolytic adenovirus application.

Keywords

References

  1. Blackwell JL, Miller CR, Douglas JT, Li H, Reynolds PN, Carroll WR, Peters GE, Strong TV, Curiel DT. Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1999 125: 856 -863. https://doi.org/10.1001/archotol.125.8.856
  2. Brough DE, Lizonova A, Hsu C, Kulesa VA, Kovesdi I. A gene transfer vector-cell line system for complete functional complementation of adenovirus early regions E1 and E4. J Virol. 1996. 70: 6497-6501.
  3. Cho WK, Seong YR, Lee YH, Kim MJ, Hwang KS, Yoo J, Choi S, Jung CR, Im DS. Oncolytic effects of adenovirus mutant capable of replicating in hypoxic and normoxic regions of solid tumor. Molecular therapy: the journal of the American Society of Gene Therapy. 2004. 10: 938-949. https://doi.org/10.1016/j.ymthe.2004.07.023
  4. Cripe TP, Dunphy EJ, Holub AD, Saini A, Vasi NH, Mahller YY, Collins MH, Snyder JD, Krasnykh V, Curiel DT. Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. Cancer Res. 2001. 61: 2953-2960.
  5. Flomenberg PR, Chen M, Munk G, Horwitz MS. Molecular epidemiology of adenovirus type 35 infections in immunocompromised hosts. J Infect Dis. 1987. 155: 1127-1134. https://doi.org/10.1093/infdis/155.6.1127
  6. Garcia-Castro J, Segovia JC, Garcia-Sanchez F, Lillo R, Gomez- Navarro J, Curiel DT, Bueren JA. Selective transduction of murine myelomonocytic leukemia cells (WEHI- 3B) with regular and RGD-adenoviral vectors. Mol Ther. 2001. 3: 70-77. https://doi.org/10.1006/mthe.2000.0221
  7. Gonzalez R, Vereecque R, Wickham TJ, Facon T, Hetuin D, Kovesdi I, Bauters F, Fenaux P, Quesnel B. Transduction of bone marrow cells by the AdZ.F (pK7) modified adenovirus demonstrates preferential gene transfer in myeloma cells. Hum Gene Ther. 1999. 10: 2709-2717. https://doi.org/10.1089/10430349950016753
  8. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967. 26: 365-369 https://doi.org/10.1016/0022-2836(67)90307-5
  9. Jee YS, Lee SG, Lee JC, Kim MJ, Lee JJ, Kim DY, Park SW, Sung MW, Heo DS. Reduced expression of coxsackievirus and adenovirus receptor (CAR) in tumor tissue compared to normal epithelium in head and neck squamous cell carcinoma patients. Anticancer Res. 2002. 22: 2629-2634.
  10. Kasono K, Blackwell JL, Douglas JT, Dmitriev I, Strong TV, Reynolds P, Kropf DA, Carroll WR, Peters GE, Bucy RP. Selective gene delivery to head and neck cancer cells via an integrin targeted adenoviral vector. Clin Cancer Res. 1999. 5: 2571-2579.
  11. MacKenzie KL, Hackett NR, Crystal RG, Moore MA. Adenoviral vector-mediated gene transfer to primitive human hematopoietic progenitor cells: assessment of transduction and toxicity in long-term culture. Blood. 2000. 96: 100-108.
  12. Miller CR, Buchsbaum DJ, Reynolds PN, Douglas JT, Gillespie GY, Mayo MS, Raben D, Curiel DT. Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res. 1998. 58: 5738-5748.
  13. Okegawa T, Li Y, Pong RC, Bergelson JM, Zhou J, Hsieh JT. The dual impact of coxsackie and adenovirus receptor expression on human prostate cancer gene therapy. Cancer Res. 2000. 60: 5031-5036.
  14. Okegawa T, Pong RC, Li Y, Bergelson JM, Sagalowsky AI, Hsieh JT. The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of car protein structure. Cancer Res. 2001. 61: 6592-6600.
  15. Pipiya T, Sauthoff H, Huang YQ, Chang B, Cheng J, Heitner S, Chen S, Rom WN, Hay JG. Hypoxia reduces adenoviral replication in cancer cells by downregulation of viral protein expression. Gene Therapy. 2005. 12: 911-917. https://doi.org/10.1038/sj.gt.3302459
  16. Post DE, Devi NS, Li Z, Brat DJ, Kaur B, Nicholson A, Olson JJ, Zhang Z, Van Meir EG. Cancer therapy with a replicating oncolytic adenovirus targeting the hypoxic microenvironment of tumors. Clinical cancer research: an official journal of the American Association for Cancer Research. 2004. 10: 8603 -8612. https://doi.org/10.1158/1078-0432.CCR-04-1432
  17. Segerman A, Atkinson JP, Marttila M, Dennerquist V, Wadell G, Arnberg N. Adenovirus type 11 uses CD46 as a cellular receptor. J Virol. 2003. 77: 9183-9191. https://doi.org/10.1128/JVI.77.17.9183-9191.2003
  18. Segerman A, Mei YF, Wadell G. Adenovirus types 11p and 35p show high binding efficiencies for committed hematopoietic cell lines and are infective to these cell lines. J Virol. 2000. 74: 1457-1467. https://doi.org/10.1128/JVI.74.3.1457-1467.2000
  19. Stecher H, Shayakhmetov DM, Stamatoyannopoulos G, Lieber A. A capsid-modified adenovirus vector devoid of all viral genes: assessment of transduction and toxicity in human hematopoietic cells. Mol Ther. 2001. 4: 36-44. https://doi.org/10.1006/mthe.2000.0410
  20. van der Poel HG, Molenaar B, van Beusechem VW, Haisma HJ, Rodriguez R, Curiel DT, Gerritsen WR. Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder cancer. J Urol. 2002. 168: 266-272. https://doi.org/10.1016/S0022-5347(05)64905-1
  21. Vanderkwaak TJ, Wang M, Gomez-Navarro J, Rancourt C, Dmitriev I, Krasnykh V, Barnes M, Siegal GP, Alvarez R, Curiel DT. An advanced generation of adenoviral vectors selectively enhances gene transfer for ovarian cancer gene therapy approaches. Gynecol Oncol. 1999. 74: 227-234. https://doi.org/10.1006/gyno.1999.5432
  22. Vogels R, Zuijdgeest D, van Rijnsoever R, Hartkoorn E, Damen I, de Bethune MP, Kostense S, Penders G, Helmus N, Koudstaal W. Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity. J Virol. 2003. 77: 8263-8271. https://doi.org/10.1128/JVI.77.15.8263-8271.2003
  23. Wickham TJ, Roelvink PW, Brough DE, Kovesdi I. Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nat Biotechnol. 1996. 14: 1570-1573. https://doi.org/10.1038/nbt1196-1570