PMID- 17520672
OWN - NLM
STAT- MEDLINE
DCOM- 20071108
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 121
IP  - 6
DP  - 2007 Sep 15
TI  - Interferon-gamma regulation of TNFalpha-induced matrix metalloproteinase 3 
      expression and migration of human glioma T98G cells.
PG  - 1190-6
AB  - Induction of proinflammatory cytokines in response to malignant cells is an 
      integral component of immune response to control tumor development. However, 
      recent evidences have suggested that tumor cells may evade the immune system and 
      exploit inflammatory responses to enhance its own growth. An exemplary example is 
      the highly invasive and tumor necrosis factor (TNF)alpha-resistant glioblastoma, 
      whose growth is associated with TNFalpha expression. We thus examined whether the 
      tumor takes advantage of TNFalpha overexpression to enhance its invasiveness. To 
      delineate the contribution of inflammation in tumor migration, we demonstrated 
      that the role of proinflammatory cytokines on matrix metalloproteinases-3 (MMP-3) 
      expression, and its consequent effects on the invasiveness of a human glioma 
      cell-line, T98G. By using Matrigel Invasion Chamber, T98G cell migration was 
      significantly enhanced in response to TNFalpha. In contrast, interferon-gamma 
      (IFN gamma) reduced both basal and TNFalpha-enhanced cell invasion. To 
      investigate the mechanisms involved, we demonstrated that TNFalpha upregulated 
      mRNA and protein expression of MMP-3 in T98G cells, whereas IFN gamma 
      downregulated the MMP-3 expression. The role of MMP-3 in glioma invasiveness was 
      further confirmed by transfecting MMP-3 siRNA in T98G to abrogate the 
      TNFalpha-enhanced cell invasion. To delineate the mechanisms further, we showed 
      that IFN gamma exerts an inhibitory effect on the binding of TNFalpha-activated 
      Ets-1 and NF kappa B to their respective enhancer elements found in MMP-3 
      promoter. In summary, our results indicated that TNFalpha enhances the 
      invasiveness of T98G glioma cells through MMP-3 induction, and such enhancement 
      of cell migration can be inhibited by IFN gamma.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Cheng, Sherman M
AU  - Cheng SM
AD  - Immunology Research Laboratory, Department of Paediatrics and Adolescent 
      Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
FAU - Xing, Bing
AU  - Xing B
FAU - Li, James C B
AU  - Li JC
FAU - Cheung, Benny K W
AU  - Cheung BK
FAU - Lau, Allan S Y
AU  - Lau AS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement/*physiology
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression
MH  - Glioma/immunology/*metabolism
MH  - Humans
MH  - Interferon-gamma/immunology/*metabolism
MH  - Matrix Metalloproteinase 3/*biosynthesis/immunology
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/immunology/*metabolism
EDAT- 2007/05/24 09:00
MHDA- 2007/11/09 09:00
CRDT- 2007/05/24 09:00
PHST- 2007/05/24 09:00 [pubmed]
PHST- 2007/11/09 09:00 [medline]
PHST- 2007/05/24 09:00 [entrez]
AID - 10.1002/ijc.22729 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Sep 15;121(6):1190-6. doi: 10.1002/ijc.22729.