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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2016 ; 11
(11
): e0166164
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Intracellular Iron Chelation Modulates the Macrophage Iron Phenotype with
Consequences on Tumor Progression
#MMPMID27806101
Mertens C
; Akam EA
; Rehwald C
; Brüne B
; Tomat E
; Jung M
PLoS One
2016[]; 11
(11
): e0166164
PMID27806101
show ga
A growing body of evidence suggests that macrophage polarization dictates the
expression of iron-regulated genes. Polarization towards iron sequestration
depletes the microenvironment, whereby extracellular pathogen growth is limited
and inflammation is fostered. In contrast, iron release contributes to cell
proliferation, which is important for tissue regeneration. Moreover, macrophages
constitute a major component of the infiltrates in most solid tumors. Considering
the pivotal role of macrophages for iron homeostasis and their presence in
association with poor clinical prognosis in tumors, we approached the possibility
to target macrophages with intracellular iron chelators. Analyzing the expression
of iron-regulated genes at mRNA and protein level in primary human macrophages,
we found that the iron-release phenotype is a characteristic of polarized
macrophages that, in turn, stimulate tumor cell growth and progression. The
application of the intracellular iron chelator (TC3-S)2 shifted the macrophage
phenotype from iron release towards sequestration, as determined by the iron-gene
profile and atomic absorption spectroscopy (AAS). Moreover, whereas the addition
of macrophage supernatants to tumor cells induced tumor growth and metastatic
behavior, the supernatant of chelator-treated macrophages reversed this effect.
Iron chelators demonstrated potent anti-neoplastic properties in a number of
cancers, both in cell culture and in clinical trials. Our results suggest that
iron chelation could affect not only cancer cells but also the tumor
microenvironment by altering the iron-release phenotype of tumor-associated
macrophages (TAMs). The study of iron chelators in conjunction with the effect of
TAMs on tumor growth could lead to an improved understanding of the role of iron
in cancer biology and to novel therapeutic avenues for iron chelation approaches.
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