PMID- 19306372
OWN - NLM
STAT- MEDLINE
DCOM- 20091030
LR  - 20220408
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 57
IP  - 13
DP  - 2009 Oct
TI  - Stat3 inhibition activates tumor macrophages and abrogates glioma growth in mice.
PG  - 1458-67
LID - 10.1002/glia.20863 [doi]
AB  - As the main effector-cell population of the central nervous system, microglia 
      (MG) are considered to play an important immunoregulatory function in a number of 
      pathological conditions such as inflammation, trauma, degenerative disease, and 
      brain tumors. Recent studies, however, have suggested that the anti-neoplastic 
      function of MG may be suppressed in malignant brain tumors. Considering the 
      proposed suppressive role of signal transducers and activators of transcription 3 
      (Stat3) in antitumor immunity, we evaluated the role of Stat3 inhibition on MG 
      and macrophage (MP) activation and tumor growth in a murine glioma model. N9 MG 
      cells were exposed to GL261 glioma conditioned medium (GL261-CM) and evaluated 
      for Stat3 activity and cytokine expression. Furthermore, the role of Stat3 
      inhibition on MG and MP activation was studied both in vitro and in vivo. 
      Finally, the effect of Stat3 inhibition on tumor growth was assessed in 
      intracranial GL261 gliomas. GL261-CM increased Stat3 activity in N9 cells in 
      vitro and resulted in overexpression of IL-10 and IL-6, and downregulation of 
      IL1-beta, a pro-inflammatory cytokine. Inhibition of Stat3 by CPA-7 or siRNA 
      reversed glioma-induced cytokine expression profile in N9 cells. Furthermore, 
      inactivation of Stat3 in intracranial GL261 tumors by siRNA resulted in MG/MP 
      activation and tumor growth inhibition. Glioma-induced MG and MP suppression may 
      be mediated thorough Stat3. Inhibition of Stat3 function in tumor MG/MP may 
      result in their activation and can potentially be used as an adjunct 
      immunotherapy approach for gliomas.
FAU - Zhang, Leying
AU  - Zhang L
AD  - Division of Neurosurgery, Beckman Research Institute, City of Hope Medical 
      Center, Duarte, California, USA.
FAU - Alizadeh, Darya
AU  - Alizadeh D
FAU - Van Handel, Michelle
AU  - Van Handel M
FAU - Kortylewski, Marcin
AU  - Kortylewski M
FAU - Yu, Hua
AU  - Yu H
FAU - Badie, Behnam
AU  - Badie B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Chlorine Compounds)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Platinum Compounds)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (trichloronitritodiammineplatinum(IV))
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Brain Neoplasms/pathology/physiopathology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Chlorine Compounds/pharmacology
MH  - Culture Media, Conditioned
MH  - Glioma/pathology/*physiopathology
MH  - Interleukin-10/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Macrophages/*physiology
MH  - Mice
MH  - Microglia/physiology
MH  - Neoplasm Transplantation
MH  - Platinum Compounds/pharmacology
MH  - RNA, Small Interfering
MH  - STAT3 Transcription Factor/*antagonists & inhibitors/metabolism
EDAT- 2009/03/24 09:00
MHDA- 2009/10/31 06:00
CRDT- 2009/03/24 09:00
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/10/31 06:00 [medline]
AID - 10.1002/glia.20863 [doi]
PST - ppublish
SO  - Glia. 2009 Oct;57(13):1458-67. doi: 10.1002/glia.20863.