A study of angiogenesis in head and neck cancers and its application to cancer gene therapy

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Vascular endothelial growth factor (VEGF) gene was transfected to the head and neck cancer cell line and the effect of gene induction on the tumor growth was examined in vitro and in vivo. The results were as follows ;1. VEGF gene transfection to the head and neck cancer cell line.The maxillary cancer cell line expressing no VEGF was established in our department and named as OKK-L N. VEGF gene expressing vector was transfected to OKK-LN cell line, and OKK-LN/pCIneo-VEGF which producing VEGF was established. This ceU line intensively expressed VEGF compared with the control cell line, OKK-LN/pCIneo transfected only pCIneo plasmid.2. Tumor cell growth of the VEGF-transfectd cells transplanted to nude mouse.Both cell lines transplanted to 6 week Balb/c nu/nu mice by subcutaneous injection to right lateral abdomen. Tumor volume of the VEGF-transfected group (OKK-LN/pCIneo-VEGF ; n = 6) showed approximately three times larger than the controlled group (OKK-LN/pCIneo ; n = 8) at Day 35 after the transplantation. The survival of the VEGF-transfected group was shorter by 9 days in average compared to the control group.3. Inhibition of the tumor growth by the angiogenesis suppression factor.The effect of TNP-470, Fumagilin analogue, which nonspecifically inhibits angiogenesis induced by the angiogenesis proliferating factors, such as VEGF and bFGF on the growth of VEGF producing tumor was examined. TNP-470 was simultaneously administered to nude mice at the time of transplantation of OKK-LN/pCIneo-VEGF. Tumor volume of TNP-470 administered group (n = 5) was significantly reduced to one-third compared with non-administered group (n = 5) at Day 35 and Day 42 after the transplantation. And the survival of TNP-470 administered group was significantly prolonged.In conclusion, the angiogenesis plays important roles on cancer cell growth, metastasis and survival in head and neck cancer.