PMID- 23469193
OWN - NLM
STAT- MEDLINE
DCOM- 20130827
LR  - 20220309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian 
      tumors: possible implication for ovarian tumor intervention.
PG  - e57436
LID - 10.1371/journal.pone.0057436 [doi]
LID - e57436
AB  - The aim of this current study was to investigate the expression of the tumor 
      necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor 
      fibroblast growth factor-inducible 14 (Fn14) in human malignant ovarian tumors, 
      and test TWEAK's potential role on tumor progression in cell models in-vitro. 
      Using immunohistochemistry (IHC), we found that TWEAK and its receptor Fn14 were 
      expressed in human malignant ovarian tumors, but not in normal ovarian tissues or 
      in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression 
      was detected in the majority of malignant tumors (36 out of 41, 87.80%). 
      Similarly, 35 out of 41 (85.37%) malignant ovarian tumors were Fn14 positive. In 
      these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected 
      with patients' clinical subtype/stages or pathological features. In vitro, we 
      demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell 
      proliferation in combination with tumor necrosis factor-alpha (TNF-alpha), whereas either 
      TWEAK or TNF-alpha alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-alpha 
      production in cultured THP-1 macrophages. Meanwhile, conditioned media from 
      TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and 
      invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1) 
      production in cultured HO-8910PM cells to possibly recruit macrophages. Our 
      results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian 
      tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors 
      indicates that it might be detected as a malignant ovarian tumor marker.
FAU - Gu, Liying
AU  - Gu L
AD  - Department of Gynecology and Obstetrics, Renji Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, PR China.
FAU - Dai, Lan
AU  - Dai L
FAU - Cao, Cong
AU  - Cao C
FAU - Zhu, Jing
AU  - Zhu J
FAU - Ding, Chuanwei
AU  - Ding C
FAU - Xu, Hai-Bo
AU  - Xu HB
FAU - Qiu, Lihua
AU  - Qiu L
FAU - Di, Wen
AU  - Di W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130304
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokine TWEAK)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNFRSF12A protein, human)
RN  - 0 (TNFSF12 protein, human)
RN  - 0 (TWEAK Receptor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Necrosis Factors)
SB  - IM
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Carcinoma/*genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/agonists/genetics/metabolism
MH  - Coculture Techniques
MH  - Cytokine TWEAK
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Macrophage Activation/drug effects
MH  - Macrophages/cytology/drug effects/metabolism
MH  - Ovarian Neoplasms/*genetics/metabolism/pathology
MH  - Receptors, Tumor Necrosis Factor/*genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism/pharmacology
MH  - Signal Transduction/drug effects
MH  - TWEAK Receptor
MH  - Tumor Necrosis Factor-alpha/biosynthesis/pharmacology
MH  - Tumor Necrosis Factors/*genetics/metabolism/pharmacology
PMC - PMC3587594
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/03/08 06:00
MHDA- 2013/08/28 06:00
PMCR- 2013/03/04
CRDT- 2013/03/08 06:00
PHST- 2012/09/25 00:00 [received]
PHST- 2013/01/22 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/08/28 06:00 [medline]
PHST- 2013/03/04 00:00 [pmc-release]
AID - PONE-D-12-29477 [pii]
AID - 10.1371/journal.pone.0057436 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e57436. doi: 10.1371/journal.pone.0057436. Epub 2013 Mar 4.