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.

Quantitative Analysis of Transferrin Receptor 1 (TfR1) in Individual Breast Cancer Cells by Means of Labeled Antibodies and Elemental (ICP-MS) Detection

“…Such a finding confirms that quickly proliferating cells, such as MDA-MB-231, express TfR1 at very high levels, and this expression can even increase in response to iron deficiencies, which is also sustained by previous measurements of the intracellular Fe concentration in these two models . This shows the importance of the developed methodology that could be further implemented for the absolute measurement of other malignancy biomarkers at the single-cell level with high sensitivity and minimum sample handling (no need for cell lysis).…”

Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection

“…DI is stable in serum with particle uptake and iron extraction facilitated by macrophages, as described above [ 5 , 8 ]. While many analytical methods are available in the literature for the determination of iron [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], no suitable analytical method was available for accurately measuring all iron forms including total iron (TI), TBI, NTBI, and DI in a pharmacokinetic rat study. A few discrete methods were reported for determination of free iron and TBI.…”

Mechanism of Ferritin Heavy Chain in the Proliferation and Migration of Prostate Cancer Cells

“…3). 4. Successfully constructed lentivirus-mediated FTH overexpression cell lines (DU145-FTH + , LNCaP-FTH + ) and negative control groups (DU145-FTH NC , LNCaP-FTH NC ).…”

“…It is a nanoprotein composed of 24 subunits variably assembled including ferritin heavy chain (FTH) and ferritin light chain (FTL) [3]. One of the main characteristics of ferritin is its ability to absorb iron ions and induce its mineralization by utilizing its ferrioxidase activity and chemical properties speci c to the cavity environment [4]. The two subunits of ferritin: the heavy chain (FTH) has feroxidase and antioxidant activity, which can convert toxic ferrous ions into less toxic iron ions [5,6].…”