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Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma
T Nakashima1, J M Hudson, G L Clayman
1Department of Head and Neck Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Background:
Vascular endothelial growth factor (VEGF) is a potent paracrine angiogenic factor involved in angiogenesis. We determined whether antisense VEGF transfection can suppress angiogenic activity of a human squamous cell carcinoma of the head and neck (SCCHN) cell line.
Methods:
Human SCCHN cell lines were screened for VEGF secretion by ELISA. The highest VEGF secreting cell line was transfected with an antisense VEGF vector. Endothelial cell migration assays were performed using the conditioned medium from the transfected clones. Tumorigenicity assays of the transfectants in nude mice were also performed.
Results:
Antisense VEGF expression exhibited a 20-fold inhibition of VEGF secretion. The addition of conditioned medium from the antisense clones resulted in 50% reduction of endothelial migration. There was no effect on in vivo tumorigenicity.
Conclusions:
Antisense VEGF transfection effectively down-regulated VEGF secretion from SCCHN cells that had high VEGF secretion. Targeting VEGF expression may be useful for suppressing angiogenesis in head and neck cancer.
Insights
Antisense VEGF transfection significantly reduced vascular endothelial growth factor (VEGF) secretion in head and neck cancer cells. This approach shows potential for suppressing tumor angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, crucial for tumor growth.
- Squamous cell carcinoma of the head and neck (SCCHN) is known to secrete VEGF.
- Understanding VEGF's role in SCCHN is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the efficacy of antisense VEGF transfection in suppressing angiogenic activity of SCCHN cells.
- To determine if down-regulating VEGF impacts endothelial cell migration and tumor growth in vivo.
Main Methods:
- Screening of human SCCHN cell lines for VEGF secretion using ELISA.
- Transfection of high-VEGF secreting SCCHN cells with an antisense VEGF vector.
- Assessing endothelial cell migration using conditioned medium from transfected cells and evaluating tumor growth in nude mice.
Main Results:
- Antisense VEGF transfection led to a 20-fold reduction in VEGF secretion.
- Conditioned medium from antisense clones reduced endothelial cell migration by 50%.
- No significant impact on in vivo tumor growth was observed.
Conclusions:
- Antisense VEGF transfection effectively down-regulates VEGF secretion in SCCHN cells.
- Targeting VEGF expression presents a promising strategy for inhibiting angiogenesis in head and neck cancers.
- Further research is needed to explore the in vivo therapeutic potential.