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Updated: Aug 9, 2026
DNA Vector-based RNA Interference to Study Gene Function in Cancer
Published on: June 4, 2012
Development of lentiviral vectors for antiangiogenic gene delivery
T Shichinohe1, B H Bochner, K Mizutani
1Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Abstract:
Growth and metastasis of malignant tumors requires angiogenesis. Inhibition of tumor-induced angiogenesis may represent an effective cytostatic strategy. We have constructed recombinant self-inactivating lentiviral vectors expressing angiostatin and endostatin, and have tested their antiangiogenic activities. As VSV-G-pseudotyped lentiviral vectors showed low relative transduction titers on bovine aortic and human umbilical vein endothelial cells, it was difficult to achieve significant inhibition of endothelial cell growth by lentivirus-mediated antiangiogenic gene transfer directly to endothelial cells without concomitant vector-associated cytotoxicity. However, lentivirus vectors could efficiently and stably transduce T24 human bladder cancer cells that are relatively resistant to adenovirus infection due to loss of coxsackievirus-adenovirus receptor expression. Long-term expression and secretion of angiostatin and endostatin from lentivirus-transduced T24 cells resulted in significant inhibition of cellular proliferation on coculture with endothelial cells. This report represents the first use of lentivirus-based vectors to deliver the antiangiogenic factors, angiostatin and endostatin, and suggests the potential utility of antiangiogenic gene therapy with lentiviral vectors for the treatment of cancer.
Insights
This study shows lentiviral vectors can deliver antiangiogenic genes, angiostatin and endostatin, to cancer cells. This approach inhibits tumor growth and offers potential for cancer gene therapy.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Tumor growth and metastasis depend on angiogenesis.
- Inhibiting tumor-induced angiogenesis is a potential cytostatic cancer treatment strategy.
Purpose of the Study:
- To construct and test lentiviral vectors for delivering antiangiogenic factors, angiostatin and endostatin.
- To evaluate the efficacy of lentivirus-mediated gene transfer for cancer therapy.
Main Methods:
- Recombinant self-inactivating lentiviral vectors were engineered to express angiostatin and endostatin.
- Transduction efficiency was assessed in endothelial cells and T24 human bladder cancer cells.
- Antiangiogenic activity was evaluated by co-culturing transduced cancer cells with endothelial cells.
Main Results:
- VSV-G-pseudotyped lentiviral vectors showed low transduction titers on endothelial cells, limiting direct antiangiogenic gene transfer.
- Lentiviral vectors efficiently transduced T24 human bladder cancer cells, which are resistant to adenovirus.
- Long-term expression of angiostatin and endostatin from transduced T24 cells significantly inhibited endothelial cell proliferation in co-culture.
Conclusions:
- Lentiviral vectors can be effectively used to deliver antiangiogenic factors, angiostatin and endostatin.
- This study demonstrates the potential of lentiviral vectors for antiangiogenic gene therapy in cancer treatment.
- Cancer cells can serve as effective delivery vehicles for sustained release of therapeutic antiangiogenic proteins.
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