PMID- 20427344
OWN - NLM
STAT- MEDLINE
DCOM- 20101110
LR  - 20211203
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 31
IP  - 10
DP  - 2010 Oct
TI  - Knockout of HIF-1alpha in tumor-associated macrophages enhances M2 polarization and 
      attenuates their pro-angiogenic responses.
PG  - 1863-72
LID - 10.1093/carcin/bgq088 [doi]
AB  - Tumor-associated macrophages (TAMs) constitute major infiltrates of solid tumors 
      and express a marker profile that characterizes alternatively activated 
      macrophages (Mcapital EF, Cyrillics). TAMs accumulate in hypoxic tumor regions, express high amounts 
      of hypoxia-inducible factor-1 (HIF-1) and contribute to tumor angiogenesis and 
      invasiveness. However, the precise role of HIF-1 on Mcapital EF, Cyrillic infiltration and phenotype 
      alterations remains poorly defined. Therefore, we cocultured wild type (wt) 
      versus HIF-1alpha(-/-) Mcapital EF, Cyrillics with tumor spheroids. Both, wt and HIF-1alpha(-/-) Mcapital EF, Cyrillics, 
      infiltrated hypoxic regions of tumor spheroids at equal rates and got 
      alternatively activated. Interestingly, significantly higher amounts of 
      HIF-1alpha(-/-) Mcapital EF, Cyrillics expressed the TAM markers CD206 and stabilin-1 compared with wt 
      phagocytes. Stimulation of infiltrated TAMs with lipopolysaccharide 
      (LPS)/interferon-gamma revealed a reduced expression of the pro-inflammatory markers 
      interleukin (IL)-6, tumor necrosis factor-alpha and inducible nitric oxide synthase 
      in HIF-1alpha(-/-) Mcapital EF, Cyrillics. Furthermore, HIF-1alpha(-/-) Mcapital EF, Cyrillics were less cytotoxic toward tumor 
      cells. Although infiltration of Mcapital EF, Cyrillics increased the invasive potential of tumor 
      spheroids independently of HIF-1, the ability to stimulate differentiation of 
      stem cells toward CD31-positive cells was triggered by wt but not by HIF-1alpha(-/-) 
      Mcapital EF, Cyrillics. Our data suggest that HIF-1alpha-deficient Mcapital EF, Cyrillics develop a more prominent TAM 
      marker profile accompanied by reduced cytotoxicity, whereas HIF-1 seems 
      indispensable for the angiogenesis-promoting properties of TAMs.
FAU - Werno, Christian
AU  - Werno C
AD  - Institute of Biochemistry I--Pathobiochemistry/Zentrum fur Arzneimittelforschung, 
      Entwicklung und Sicherheit, Faculty of Medicine, Goethe-University Frankfurt, 
      Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
FAU - Menrad, Heidi
AU  - Menrad H
FAU - Weigert, Andreas
AU  - Weigert A
FAU - Dehne, Nathalie
AU  - Dehne N
FAU - Goerdt, Sergij
AU  - Goerdt S
FAU - Schledzewski, Kai
AU  - Schledzewski K
FAU - Kzhyshkowska, Julia
AU  - Kzhyshkowska J
FAU - Brune, Bernhard
AU  - Brune B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100428
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Cell Adhesion Molecules, Neuronal)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-6)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Lymphocyte Homing)
RN  - 0 (STAB1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules, Neuronal/analysis
MH  - Cell Line, Tumor
MH  - *Cell Polarity
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-6/biosynthesis
MH  - Lectins, C-Type/analysis
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*physiology
MH  - Mannose Receptor
MH  - Mannose-Binding Lectins/analysis
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Neoplasms/*blood supply/pathology
MH  - Neovascularization, Pathologic/*etiology
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - Platelet Endothelial Cell Adhesion Molecule-1/analysis
MH  - Receptors, Cell Surface/analysis
MH  - Receptors, Lymphocyte Homing/analysis
MH  - Spheroids, Cellular/pathology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2010/04/30 06:00
MHDA- 2010/11/11 06:00
CRDT- 2010/04/30 06:00
PHST- 2010/04/30 06:00 [entrez]
PHST- 2010/04/30 06:00 [pubmed]
PHST- 2010/11/11 06:00 [medline]
AID - bgq088 [pii]
AID - 10.1093/carcin/bgq088 [doi]
PST - ppublish
SO  - Carcinogenesis. 2010 Oct;31(10):1863-72. doi: 10.1093/carcin/bgq088. Epub 2010 
      Apr 28.