Abstract
To investigate the efficiency of suicide gene systems on vascular cells, HSV-tk/GCV and EC-CD/5-FC systems were established on vascular endothelial cells in vitro by retroviral transduction. Both modified cell lines were highly sensitive to prodrugs, the IC50 for GCV was less than 0.4 μM, and IC50 for 5-FC was less than 75 μM, while the parental endothelial cells were insensitive even at the highest concentrations of prodrugs in this experiment. Mixed cellular assay showed that significant bystander effect was exhibited in modified endothelial cells. When only 10% or 30% of the mixed cells were tk positive and exposed to 20 μM GCV for 6 days, more than 60% or 90% of the whole population was killed. Similar result was also found in CD positive cells. These results indicated that both HSV-tk/GCV and EC-CD/5-FC systems could efficiently suppress endothelial cell growth in vitro.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- (GCV):
-
ganciclovir
- (5-FC):
-
5-fluorocytosine
- (tk):
-
thymidine kinase
- (CD):
-
cytosine deaminase
References
Filder IJ, Ellis LM . The implication of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994; 79:185–8.
Folkman J . Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285:1182–6.
Fan TP, Jaggar R, Bicknell R . Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy. Trends Pharmacol. Sci 1995;16(2):57–66.
Dong QG, Bernasconi S, Lostaglio S, Calmanocici RW, Padura IM, Breviario F, et al. A general strategy for isolation of endothelial cells from murine tissues: characteri-zation of two endothelial cell lines obtained from murine lung and subcutaneous sponge implants. Arterioscleriosis, Thrombosis, and Vascular Biology, in press.
Bi WL, Parysek LM, Warnick R, Stambrook PJ . In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy. Hum Gene Ther 1993;4(6):725–31.
Robert RE, Thierry PC, Bruce RP, Margaret AB, Candace SJ, Ruth AM, et al. Gene therapy and endothelial cell targeting for cancer. Ann NY. Acad Sci 1994; 176:257–64.
John DP . Cancer gene therapy: a bystander effect using the gap junctional pathway. Mol Carcinogen 1994; 11:127–30.
Pitts JD, Kam E, Morgan D . The role of junctional communication in cellular growth control and tumorigenesis. Modern Cell Biol 1992; 7:397–409.
Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM . In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 1992; 256:1550–2.
Ram Z, Culver K, Walbridge S, Blaese R, Oldfield E . In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 1993; 53:83–8.
Folkman J . The role of angiogenesis in tumor growth. Semin Cancer Biol 1992; 3:65–71.
Hobson B, Denekamp J . Endothelial proliferation in tumors and normal tissues: continuous labelling studies. Br J Cancer 1984;49(4):405–13.
Kaoru M, Daniel EJ, Lewis TW . A novel promoter for vascular endothelial growth factor receptor (flt-l) that confers endothelial-specific gene expression. J Bio Chem 1995;270(46):27948–53.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Xu, L., Xu, D., Ge, K. et al. The use of suicide gene systems in vascular cells in vitro. Cell Res 8, 73–78 (1998). https://doi.org/10.1038/cr.1998.8
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/cr.1998.8