Iron speciation, ferritin concentrations and Fe : ferritin ratios in different malignant breast cancer cell lines: on the search for cancer biomarkers

Abstract

Iron is an essential element for cell growth and division. Recent experiments have linked a deregulation of iron's metabolism with breast cancer progression, aggressiveness and recurrence. In fact, it is conceived that chronic failure in the redox balance due to the presence of a high intracellular concentration of this metal has the potential to modulate specific signaling networks associated with cancer malignancy. Thus, this work has been focused on the comparative evaluation of part of the Fe metallome in two breast cancer cell lines of different malignancies: MCF-7 and MDA-MB-231. Evaluation of the total cytosolic iron content as well as the ultrafiltrable iron content has been conducted using inductively coupled plasma mass spectrometry (ICP-MS) as a Fe selective detector. The obtained results revealed a significantly higher total Fe concentration in the less malignant phenotype. Additionally, Fe-fractionation experiments, conducted by coupling size exclusion chromatography (SEC) to ICP-MS showed a similar Fe distribution (speciation) in both cell phenotypes. However, further specific ferritin measurement using immunochemical based ICP-MS assays showed important differences regarding the total protein content among cell lines and, most importantly, significant differences in the Fe-content of the ferritin molecules between cell lines. This finding points out an iron-storage independent function also associated with ferritin in the most malignant phenotype of the evaluated breast cancer cells that stresses the interest in this molecule as a cancer biomarker.