TY  - JOUR
A1  - Jung, Michaela
A1  - Weigert, Andreas
A1  - Mertens, Christina
A1  - Rehwald, Claudia
A1  - Brüne, Bernhard
T1  - Iron handling in tumor-associated macrophages—is there a new role for lipocalin-2?
T2  - Frontiers in immunology
N2  - Carcinogenesis is a multistep process. Besides somatic mutations in tumor cells, stroma-associated immunity is a major regulator of tumor growth. Tumor cells produce and secrete diverse mediators to create a local microenvironment that supports their own survival and growth. It is becoming apparent that iron acquisition, storage, and release in tumor cells is different from healthy counterparts. It is also appreciated that macrophages in the tumor microenvironment acquire a tumor-supportive, anti-inflammatory phenotype that promotes tumor cell proliferation, angiogenesis, and metastasis. Apparently, this behavior is attributed, at least in part, to the ability of macrophages to support tumor cells with iron. Polarization of macrophages by apoptotic tumor cells shifts the profile of genes involved in iron metabolism from an iron sequestering to an iron-release phenotype. Iron release from macrophages is supposed to be facilitated by ferroportin. However, lipid mediators such as sphingosine-1-phosphate, released form apoptotic tumor cells, upregulate lipocalin-2 (Lcn-2) in macrophages. This protein is known to bind siderophore-complexed iron and thus, may participate in iron transport in the tumor microenvironment. We describe how macrophages handle iron in the tumor microenvironment, discuss the relevance of an iron-release macrophage phenotype for tumor progression, and propose a new role for Lcn-2 in tumor-associated macrophages.
KW  - apoptosis
KW  - phagocytosis
KW  - macrophage polarization
KW  - sphingosine-1-phosphate
KW  - lipocalin-2
KW  - tumor progression
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46355
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463550
SN  - 1664-3224
N1  - Copyright: © 2017 Jung, Weigert, Mertens, Rehwald and Brüne. 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) or licensor 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.
VL  - 8
IS  - Art. 1171
SP  - 1
EP  - 12
PB  - Frontiers Media
CY  - Lausanne
ER  -