Abstract 1108: Ferritin binds breast cancer cells and tissue, and promotes proliferation independently of iron content

Abstract

Abstract A connection between iron and breast tumorigenesis has been convincingly argued over the years. Several in vivo studies have demonstrated that iron-rich diets increase tumor incidence rate in carcinogen-induced mammary tumor models. Moreover, a large cohort study has recently associated mutations in the hemochromatosis (HFE) gene (promoting iron overload) with breast cancer risk in females. Individuals with mutations in the HFE protein can exhibit iron accumulation in the liver, high transferrin saturation levels, and elevated serum ferritin levels, but not have clinical hemochromatosis. Cells store iron in ferritin, but this protein is also secreted and is detected circulating in serum. Although serum ferritin has been used as an indicator of total body iron, a specific functional role has not been proposed thus far other than perhaps recycling iron to the bone marrow. Interestingly, serum ferritin levels have been shown to be increased in breast cancer patients, and higher levels seem to be associated with poorer prognosis. Furthermore, comparisons between pre- and post-surgery ferritin levels suggested that the tumor itself is responsible for the high levels of serum ferritin possibly through secretion. We have demonstrated that ferritin binds to breast tumor sections obtained from biopsy. Based on these observations, we hypothesized that serum ferritin interacts directly with breast cancer cells enhancing their growth. In this study we report that ferritin exposure will increase proliferation and DNA synthesis in the breast cancer cell lines, MCF-7 and T47D. These effects were not dependent on the iron content of ferritin, as both apo- and holo-ferritin had comparable effects. Because extra-cellular ferritin has been speculated to play an iron delivery role in some cells, we examined changes in transferrin receptor levels, and the quenching of the fluorescent metal-sensitive dye calcein following ferritin treatments. Our data, suggests that ferritin does not deliver iron to cells, and might have an iron-independent signaling function. Taken together, these findings encourage a new perspective on serum ferritin in cancer biology, and raise several possibilities for novel therapeutic and diagnostic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1108. doi:10.1158/1538-7445.AM2011-1108