Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma.
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.
Nakashima
T
T
Department of Head and Neck Surgery, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Hudson
J M
JM
Clayman
G L
GL
D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology; D017077:Culture Media, Conditioned; D016373:DNA, Antisense / Q000235:genetics / Q000627:therapeutic use*; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D020033:Protein Isoforms / Q000037:antagonists & inhibitors* / Q000235:genetics; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D016373:DNA, Antisense; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors