PMID- 24801982
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 5
DP  - 2014
TI  - Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B 
      (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis 
      arising from colorectal cancer.
PG  - e96410
LID - 10.1371/journal.pone.0096410 [doi]
LID - e96410
AB  - Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by 
      brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and 
      is related to the poor prognosis of various malignancies. We sought to examine 
      the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) 
      tissues, its prognostic value for CRC patients, and its therapeutic potential in 
      vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used 
      to determine both BDNF and TrkB mRNA levels. The expression of these proteins in 
      their primary and metastatic tumors was investigated by immunohistochemistry. CRC 
      cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk 
      inhibitor) were used for in vitro cell viability, migration, invasion, anoikis 
      resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was 
      associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also 
      associated with lymph node metastasis. The co-expression of BDNF and TrkB was 
      associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, 
      and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF 
      increased tumor cell viability, migration, invasion and inhibited anoikis in the 
      TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice 
      injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with 
      K252a, peritoneal metastatic nodules was found to be reduced, as compared with 
      control mice. BDNF/TrkB signaling may thus be a potential target for treating 
      peritoneal carcinomatosis arising from colorectal cancer.
FAU - Tanaka, Koji
AU  - Tanaka K
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Okugawa, Yoshinaga
AU  - Okugawa Y
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Toiyama, Yuji
AU  - Toiyama Y
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Inoue, Yasuhiro
AU  - Inoue Y
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Saigusa, Susumu
AU  - Saigusa S
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Kawamura, Mikio
AU  - Kawamura M
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Araki, Toshimitsu
AU  - Araki T
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Uchida, Keiichi
AU  - Uchida K
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Mohri, Yasuhiko
AU  - Mohri Y
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
FAU - Kusunoki, Masato
AU  - Kusunoki M
AD  - Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate 
      School of Medicine, Tsu, Mie, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140506
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tropomyosin)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Caco-2 Cells
MH  - Carcinoma/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Survival/genetics
MH  - Child
MH  - Colorectal Neoplasms/*genetics/metabolism
MH  - HT29 Cells
MH  - Humans
MH  - Male
MH  - Membrane Glycoproteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Middle Aged
MH  - Peritoneal Neoplasms/*genetics/metabolism
MH  - Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Receptor, trkB
MH  - Signal Transduction/*genetics
MH  - Tropomyosin/*genetics/metabolism
MH  - Young Adult
PMC - PMC4011754
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/05/08 06:00
MHDA- 2015/01/13 06:00
PMCR- 2014/05/06
CRDT- 2014/05/08 06:00
PHST- 2013/10/15 00:00 [received]
PHST- 2014/04/07 00:00 [accepted]
PHST- 2014/05/08 06:00 [entrez]
PHST- 2014/05/08 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
PHST- 2014/05/06 00:00 [pmc-release]
AID - PONE-D-13-42235 [pii]
AID - 10.1371/journal.pone.0096410 [doi]
PST - epublish
SO  - PLoS One. 2014 May 6;9(5):e96410. doi: 10.1371/journal.pone.0096410. eCollection 
      2014.