Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms

  • Authors:
    • Malika Benouchan
    • Filipe Do Nascimento
    • Gérard Y. Perret
    • Bruno M. Colombo
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijo.28.2.457
  • Pages: 457-462
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Abstract

A current target of cancer gene therapy is tumour vasculature. We present a gene-directed enzyme prodrug therapy (GDEPT) approach to target tumours in vivo by modifying endothelial cells (ECs) with the Escherichia coli nitroreductase (ntr) gene. Firstly, we isolated two ntr-transfected clones of the human umbilical vein endothelial cell line (HUV-EC-C/ntr+) that showed a differential sensitivity in vitro to the prodrug, dinitroaziridinylbenzamide (CB1954), with respect to untransfected HUV-EC-C cells (HUV-EC-C/ntr-). Then, these cells were injected subcutaneously into nude mice, either in association with the murine melanoma cell line, B16-F10 (‘co-injected’ groups), or into tumour-bearing animals (‘post-injected’ groups). After intratumoural injection, we demonstrated, using PCR analysis, that human ECs resided in the site of the injection without spreading to other organs, such as the liver or lung. After the treatment of mice with CB1954, we observed a prolonged survival of animals carrying the HUV-EC-C/ntr+ clones with respect to control animals injected with HUV-EC-C/ntr- cells. Significant differences in tumour growth were also observed and, after immuno-histological analysis, tumours carrying HUV-EC-C/ntr+ clones showed large areas of tumour necrosis, probably due to tumour ischemia, as well as the presence of major histocompatibility complex class-II (MHC-II) positive cells. Collectively, our data indicate that targeting of the tumour vasculature by this GDEPT strategy may be an efficient approach for cancer treatment in vivo, depending on two possible bystander mechanisms based on tumour ischemia and immune cell activation.

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February 2006
Volume 28 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Benouchan M, Nascimento FD, Perret GY and Colombo BM: Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms. Int J Oncol 28: 457-462, 2006
APA
Benouchan, M., Nascimento, F.D., Perret, G.Y., & Colombo, B.M. (2006). Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms. International Journal of Oncology, 28, 457-462. https://doi.org/10.3892/ijo.28.2.457
MLA
Benouchan, M., Nascimento, F. D., Perret, G. Y., Colombo, B. M."Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms". International Journal of Oncology 28.2 (2006): 457-462.
Chicago
Benouchan, M., Nascimento, F. D., Perret, G. Y., Colombo, B. M."Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms". International Journal of Oncology 28, no. 2 (2006): 457-462. https://doi.org/10.3892/ijo.28.2.457