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Front. Oncol. | doi: 10.3389/fonc.2018.00549

Iron in the tumor microenvironment – connecting the dots

  • 1Innsbruck Medical University, Austria

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic immune activation in the setting of malignancy alters systemic iron homeostasis and directs iron fluxes into myeloid cells. While this response aims at withdrawing iron from tumor cells, it may impair the effector functions of tumor-associated macrophages and will result in iron-restricted erythropoiesis and the development of anemia, subsequently.
This review summarizes our current knowledge of the interconnections of iron homeostasis with cancer biology, discusses current clinical controversies in the treatment of anemia of cancer and focuses on the potential roles of iron in the solid tumor microenvironment, also speculating on yet unknown molecular mechanisms.

Keywords: Iron, Cancer, Hypoferremia, Anemia of cancer, Anemia of a chronic disease, Hepcidin (HAMP), fenton chemistry, Ferritin (Fer), Ferroportin (FPN), ferroptosis, Tumor-associated macrophage (TAM), Tumor-infiltrating lymphocyte (TIL)

Received: 12 Sep 2018; Accepted: 06 Nov 2018.

Edited by:

Lionel Apetoh, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Amorette Barber, Longwood University, United States
Anna K. Kozlowska, City of Hope National Medical Center, United States  

Copyright: © 2018 Pfeifhofer, Tymoszuk, Petzer, Weiss and Nairz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Manfred Nairz, Innsbruck Medical University, Innsbruck, Austria,