PMID- 21846721
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 41
DP  - 2011 Oct 14
TI  - Pigment epithelium-derived factor (PEDF) promotes tumor cell death by inducing 
      macrophage membrane tumor necrosis factor-related apoptosis-inducing ligand 
      (TRAIL).
PG  - 35943-35954
LID - S0021-9258(20)73802-0 [pii]
LID - 10.1074/jbc.M111.266064 [doi]
AB  - Pigment epithelium-derived factor (PEDF) is an intrinsic anti-angiogenic factor 
      and a potential anti-tumor agent. The tumoricidal mechanism of PEDF, however, has 
      not been fully elucidated. Here we report that PEDF induces the apoptosis of TC-1 
      and SK-Hep-1 tumor cells when they are cocultured with bone marrow-derived 
      macrophages (BMDMs). This macrophage-mediated tumor killing is prevented by 
      blockage of TNF-related apoptosis-inducing ligand (TRAIL) following treatment 
      with the soluble TRAIL receptor. PEDF also increases the amount of membrane-bound 
      TRAIL on cultured mouse BMDMs and on macrophages surrounding subcutaneous tumors. 
      PEDF-induced tumor killing and TRAIL induction are abrogated by peroxisome 
      proliferator-activated receptor gamma (PPARgamma) antagonists or small interfering RNAs 
      targeting PPARgamma. PEDF also induces PPARgamma in BMDMs. Furthermore, the activity of 
      the TRAIL promoter in human macrophages is increased by PEDF stimulation. 
      Chromatin immunoprecipitation and DNA pull-down assays confirmed that endogenous 
      PPARgamma binds to a functional PPAR-response element (PPRE) in the TRAIL promoter, 
      and mutation of this PPRE abolishes the binding of the PPARgamma-RXRalpha heterodimer. 
      Also, PPARgamma-dependent transactivation and PPARgamma-RXRalpha binding to this PPRE are 
      prevented by PPARgamma antagonists. Our results provide a novel mechanism for the 
      tumoricidal activity of PEDF, which involves tumor cell killing via 
      PPARgamma-mediated TRAIL induction in macrophages.
FAU - Ho, Tsung-Chuan
AU  - Ho TC
AD  - Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan.
FAU - Chen, Show-Li
AU  - Chen SL
AD  - Department of Microbiology, School of Medicine, National Taiwan University, 
      Taipei 100, Taiwan.
FAU - Shih, Shou-Chuan
AU  - Shih SC
AD  - Department of Gastroenterology, Mackay Memorial Hospital, Taipei 104, Taiwan; 
      Mackay Medicine, Nursing, and Management College, Taipei 112, Taiwan.
FAU - Chang, Shing-Jyh
AU  - Chang SJ
AD  - Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei 104, 
      Taiwan; Institute of Molecular and Cellular Biology, National Tsing Hua 
      University, Hsinchu 30013, Taiwan.
FAU - Yang, Su-Lin
AU  - Yang SL
AD  - Centers for Disease Control, Taipei 115, Taiwan; Department of Microbiology and 
      Immunology, National Defense Medical Center, Taipei 114, Taiwan.
FAU - Hsieh, Jui-Wen
AU  - Hsieh JW
AD  - Mackay Medicine, Nursing, and Management College, Taipei 112, Taiwan; Department 
      of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
FAU - Cheng, Huey-Chuan
AU  - Cheng HC
AD  - Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
FAU - Chen, Lee-Jen
AU  - Chen LJ
AD  - Mackay Medicine, Nursing, and Management College, Taipei 112, Taiwan; Department 
      of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
FAU - Tsao, Yeou-Ping
AU  - Tsao YP
AD  - Department of Medical Research, Mackay Memorial Hospital, Taipei 104, Taiwan; 
      Department of Microbiology and Immunology, National Defense Medical Center, 
      Taipei 114, Taiwan; Department of Ophthalmology, Mackay Memorial Hospital, Taipei 
      104, Taiwan. Electronic address: yptsao@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110816
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Eye Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 0 (Serpins)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tnfsf10 protein, mouse)
RN  - 0 (pigment epithelium-derived factor)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Eye Proteins/immunology/*metabolism
MH  - Humans
MH  - Macrophages/immunology/*metabolism
MH  - Mice
MH  - Mutation
MH  - Neoplasms/immunology/*metabolism
MH  - Nerve Growth Factors/immunology/*metabolism
MH  - PPAR gamma/immunology/metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology/metabolism
MH  - Response Elements/immunology
MH  - Retinoid X Receptor alpha/immunology/metabolism
MH  - Serpins/immunology/*metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/immunology/*metabolism
PMC - PMC3195575
EDAT- 2011/08/19 06:00
MHDA- 2011/12/14 06:00
PMCR- 2012/10/14
CRDT- 2011/08/18 06:00
PHST- 2011/08/18 06:00 [entrez]
PHST- 2011/08/19 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2012/10/14 00:00 [pmc-release]
AID - S0021-9258(20)73802-0 [pii]
AID - M111.266064 [pii]
AID - 10.1074/jbc.M111.266064 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Oct 14;286(41):35943-35954. doi: 10.1074/jbc.M111.266064. Epub 
      2011 Aug 16.