Iron: An Essential Element of Cancer Metabolism

Abstract

Cancer cells undergo considerable metabolic changes to foster uncontrolled proliferation in a hostile environment characterized by nutrient deprivation, poor vascularization and immune infiltration. While metabolic reprogramming has been recognized as a hallmark of cancer, the role of micronutrients in shaping these adaptations remains scarcely investigated. In particular, the broad electron-transferring abilities of iron make it a versatile cofactor that is involved in a myriad of biochemical reactions vital to cellular homeostasis, including cell respiration and DNA replication. In cancer patients, systemic iron metabolism is commonly altered. Moreover, cancer cells deploy diverse mechanisms to increase iron bioavailability to fuel tumor growth. Although iron itself can readily participate in redox reactions enabling vital processes, its reactivity also gives rise to reactive oxygen species (ROS). Hence, cancer cells further rely on antioxidant mechanisms to withstand such stress. The present review provides an overview of the common alterations of iron metabolism occurring in cancer and the mechanisms through which iron promotes tumor growth.

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

“…The positive APP ferritin is up-regulated under inflammatory or infectious conditions to reduce the iron accessibility of pathogenic organisms [185,186]. For numerous malignancies elevated serum ferritin concentrations have been reported as well, in part with prognostic impact [187]. Healthy human cells, foreign organisms but also cancer cells depend on iron supply for a number of cellular metabolic processes.…”

“…Healthy human cells, foreign organisms but also cancer cells depend on iron supply for a number of cellular metabolic processes. The role of iron metabolism and its regulation-partially by cells of the TME-have been reviewed excellently by Hsu et al for cancer in general [187] and by Toyokuni et al for MPM in particular, especially in context of asbestos-induced oxidative stress [188]. MPM has been associated with elevated ferritin serum levels [189][190][191], but to our knowledge the prognostic or predictive impact of ferritin has not been investigated so far.…”

“…MPM has been associated with elevated ferritin serum levels [189][190][191], but to our knowledge the prognostic or predictive impact of ferritin has not been investigated so far. However, correlations of ferritin with TAM and modulated lymphocyte function has been suggested [186,187] so in context of the APR as well as the importance of iron metabolism in MPM the study of ferritin as biomarker might reveal interesting new results. Of note, also reduction of iron storage was suggested as possible treatment target after promising preclinical results from a rat model [191,192].…”

Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors

“…As bacterial siderophores are iron carriers, the reduction in cell proliferation and cell viability of IBC cells upon drug treatment could be caused by an impairment in cellular activities due to a shortage in iron uptake. In fact, certain types of cancers can reprogram iron metabolism to allow cancer cells to survive [39]. Although therapies to block iron dependencies have been extensively studied in cancer, there are no therapies to inhibit iron uptake by cancer cells in IBC.…”

Iron at the Interface of Hepatocellular Carcinoma

“…Typically, cancer cells require iron during all stages of tumor development, survival, proliferation, and metastasis [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Molecules involved in the regulation of iron metabolism, such as transferrin receptor, ferritin H, and divalent metal transporter 1 (DMT1), are often upregulated in cancer cells in order to induce iron accumulation [ 31 , 32 ]. Observations of enhanced iron uptake and iron retention in cancer cells suggest that cancers are dependent on iron.…”