Iodine deficiency-induced long lasting angiogenic reaction in thyroid cancers occurs via a VEGF-HIF-1, but not a ROS dependent pathway.

Deficient iodine intake may be associated with increased thyroid cancer incidence. We investigated whether iodine deficiency (ID) affects angiogenic processes in thyroid malignant cells by altering the ROS-HIF-VEGF pathway. Methods: Goiters were obtained in RET/PTC3 transgenic and wild type (wt) mice and ID was induced in three thyroid carcinoma cell lines (TPC-1, 8305c, R082-w1). Thyroid blood flow, VEGF mRNA and protein, and HIF-1 protein expression were measured. The role of HIF-1 and of reactive oxygen species (ROS) was assessed. Results: The goitrogen treatment increased the thyroid blood flow in wt and RET/PTC3 mice. Compared to wt mice, basal VEGF expression was higher in RET/PTC3 mice and increased with the goitrogen treatment. In the three cell lines, ID induced a marked increase in VEGF mRNA and a moderate increase in HIF-1 protein expression which were not transient as in normal cells. ID-induced VEGF mRNA expression was fully (8305c), partially (TPC-1), or not (R082-w1) blocked by echinomycin. NAC had no effect on ID-induced VEGF mRNA and HIF-1 protein expression in the three cell lines. Conclusions: These results suggest that, in contrast with normal cells, ID-induced angiogenesis in cancer cells occurs via alternative and likely less controlled routes, thereby leading to uncontrolled growth.