PMID- 28162286
OWN - NLM
STAT- MEDLINE
DCOM- 20180110
LR  - 20220408
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 5
DP  - 2015 Aug
TI  - Macrophage Polarization In The Tumor Microenvironment.
PG  - 419
LID - S2213-2317(15)00139-1 [pii]
LID - 10.1016/j.redox.2015.09.028 [doi]
AB  - BACKGROUND: Tumor associated macrophages (TAMs) are known to support tumor 
      progression and their accumulation is generally associated with poor prognosis. 
      The shift from a tumor-attacking to a tumor-supportive macrophage phenotype is 
      based on an educational program that, at least in part, is initiated by apoptotic 
      tumor cells. AIMS: We explored the macrophage phenotype shift during tumor 
      progression by analyzing the macrophage NO-output system and examining potential 
      NO targets. METHODS: Biochemical and Molecular Biology-orientated cell culture 
      experiments, in part using 3d-tumor spheroid models as well as animal experiments 
      were used. RESULTS: Apoptotic cells polarize macrophages towards a healing, 
      tumor-supportive phenotype. Soluble mediators released from apoptotic cells, 
      among them the lipid sphingosine-1-phosphate (S1P), cause expression of arginase 
      2 in macrophages, thereby lowering citrulline/NO formation but enhancing 
      ornithine production. Mechanistically, this is achieved via the S1P2 receptor and 
      the CRE (cAMP-response element) binding site in the arginase 2 promoter. Reduced 
      NO-formation is also seen in ex vivo macrophages from a xenograft model allowing 
      restricted vs. unrestricted tumor growth based on tumor-associated S1P-formation. 
      The theoretical ability of NO to target hypoxia-inducible factor-1 (HIF-1) and 
      jumonji histone demethylases (JHDMs) in cells of the tumor microenvironment will 
      be discussed in light of the iNOS/arginase balance. Moreover, data on the 
      importance of HIF-1 in macrophages for their interaction with tumor cells, 
      polarization, and angiogenic potential will be presented. CONCLUSIONS: We 
      hypothesize that apoptotic death of tumor cells and associated macrophage 
      activation facilitates the progression of malignant disease. The macrophage 
      polarization program affects the NO-output system and the capacity of macrophages 
      to support or restrict tumor growth.
CI  - Copyright (c) 2015. Published by Elsevier B.V.
FAU - Brune, Bernhard
AU  - Brune B
AD  - Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 
      Frankfurt, Germany.
FAU - Weigert, Andreas
AU  - Weigert A
AD  - Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 
      Frankfurt, Germany.
FAU - Dehne, Nathalie
AU  - Dehne N
AD  - Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 
      Frankfurt, Germany.
LA  - eng
PT  - Journal Article
DEP - 20151230
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Neoplasm Proteins)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Humans
MH  - Macrophages/*metabolism/pathology
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Neoplasms/genetics/*metabolism/pathology
MH  - Nitric Oxide/genetics/*metabolism
MH  - *Tumor Microenvironment
EDAT- 2015/08/01 00:00
MHDA- 2015/08/01 00:01
CRDT- 2017/02/07 06:00
PHST- 2017/02/07 06:00 [entrez]
PHST- 2015/08/01 00:00 [pubmed]
PHST- 2015/08/01 00:01 [medline]
AID - S2213-2317(15)00139-1 [pii]
AID - 10.1016/j.redox.2015.09.028 [doi]
PST - ppublish
SO  - Redox Biol. 2015 Aug;5:419. doi: 10.1016/j.redox.2015.09.028. Epub 2015 Dec 30.