PMID- 20824698
OWN - NLM
STAT- MEDLINE
DCOM- 20110704
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 129
IP  - 1
DP  - 2011 Jul 1
TI  - Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction 
      of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
PG  - 122-32
LID - 10.1002/ijc.25657 [doi]
AB  - Tumor-associated macrophages (TAMs) represent alternatively activated (M2) 
      macrophages that support tumor growth. Previously, we have described a special 
      LYVE-1(+) M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset 
      identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary 
      carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein 
      expression was strongly induced in bone marrow-derived macrophages (BMDMs) by 
      combining M2 mediators (IL-4, glucocorticoids) and tumor-conditioned media (TCM). 
      Admixture of MS4A8A(+) TCM/IL-4/GC-treated BMDM significantly enhanced the tumor 
      growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced 
      overexpression of MS4A8A, Raw 264.7 macrophage-like cells displayed a special 
      gene signature. Admixture of these MS4A8A(+) Raw 264.7 cells also significantly 
      enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas. 
      To identify the signaling pathways involved in synergistic induction of MS4A8A, 
      the major signaling cascades with known functions in TAM were analyzed. Although 
      inhibitors of NF-kappaB activation and of the MAPK JNK and ERK did not show relevant 
      effects, the p38alpha/beta MAPK inhibitor SB203580 strongly and highly significantly (p 
      > 0.001) inhibited MS4A8A expression on mRNA and protein level. In addition, 
      MS4A8A expression was restricted in M2 BMDM from mice with defective GC receptor 
      (GR) dimerization indicating that classical GR gene regulation is mandatory for 
      MS4A8A induction. In conclusion, expression of MS4A8A within the complex signal 
      integration during macrophage immune responses may act to fine tune gene 
      regulation. Furthermore, MS4A8A(+) TAM may serve as a novel cellular target for 
      selective cancer therapy.
CI  - Copyright (c) 2010 UICC.
FAU - Schmieder, Astrid
AU  - Schmieder A
AD  - Department of Dermatology, Venereology and Allergology, University Medical Center 
      and Medical Faculty Mannheim, University of Heidelberg, and Center of Excellence 
      in Dermatology, Mannheim, Germany. astrid.schmieder@umm.de
FAU - Schledzewski, Kai
AU  - Schledzewski K
FAU - Michel, Julia
AU  - Michel J
FAU - Tuckermann, Jan P
AU  - Tuckermann JP
FAU - Tome, Lydia
AU  - Tome L
FAU - Sticht, Carsten
AU  - Sticht C
FAU - Gkaniatsou, Cleopatra
AU  - Gkaniatsou C
FAU - Nicolay, Jan P
AU  - Nicolay JP
FAU - Demory, Alexandra
AU  - Demory A
FAU - Faulhaber, Jorg
AU  - Faulhaber J
FAU - Kzhyshkowska, Julia
AU  - Kzhyshkowska J
FAU - Geraud, Cyrill
AU  - Geraud C
FAU - Goerdt, Sergij
AU  - Goerdt S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101128
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, CD20)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, CD20/*immunology
MH  - Cell Line
MH  - Culture Media, Conditioned
MH  - Female
MH  - Glucocorticoids/*metabolism
MH  - Immunohistochemistry
MH  - Macrophages/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, Glucocorticoid/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2010/09/09 06:00
MHDA- 2011/07/05 06:00
CRDT- 2010/09/09 06:00
PHST- 2010/06/11 00:00 [received]
PHST- 2010/08/25 00:00 [accepted]
PHST- 2010/09/09 06:00 [entrez]
PHST- 2010/09/09 06:00 [pubmed]
PHST- 2011/07/05 06:00 [medline]
AID - 10.1002/ijc.25657 [doi]
PST - ppublish
SO  - Int J Cancer. 2011 Jul 1;129(1):122-32. doi: 10.1002/ijc.25657. Epub 2010 Nov 28.