Migration Behavior of Breast Cancer Cells in the Environment of High Glucose Level and the Role of Zinc and Its Transporter

Tomoka Takatani-Nakase

The diabetes patients have been associated with an increased risk of mortality by breast cancer, and there are differences in the regimen choice and effects of breast cancer treatment between the breast cancer patients with diabetes and their nondiabetic counterparts. However, the pathophysiological relationships of diabetes and breast cancer have not yet been elucidated in detail, therefore its evaluation is strongly required to achieve novel treatment strategies for breast cancer with hyperglycemia. Extracellular circumstances of cancer cells can influence the growth and behavior, resulting in invasion, metastasis and tumor development. We demonstrated that breast cancer cells, MCF-7, cultured in hyperglycemic level significantly promotes the motile activity in comparison to normal physiological glucose level. Moreover, Zn(2+) uptake activity into cellular cytosol and the mRNA expression of zinc transporters, ZIP6 and ZIP10, in the high glucose-exposed cells were shown to be especially higher than in the physiological glucose level. The depletion of intracellular Zn(2+) by zinc chelation and ZIP6 or ZIP10 knockdown blocked the high migration activity, indicating that Zn(2+) transported via ZIP6 and ZIP10 plays an essential role in the promotion of cell motility stimulated in high glucose level. These findings provide a proposing target of the novel strategies for the diagnosis and therapy of breast cancer with hyperglycemia.