PMID- 23312550
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20130206
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 79
IP  - 3
DP  - 2013 Mar
TI  - TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large 
      cell neuroendocrine carcinoma.
PG  - 205-14
LID - S0169-5002(12)00649-6 [pii]
LID - 10.1016/j.lungcan.2012.12.004 [doi]
AB  - Tropomyosin-related kinase B (TrkB) plays an important role in tumor progression 
      in various kinds of cancers; however, little is known about biological 
      significance of TrkB in human lung cancer, especially large cell neuroendocrine 
      carcinoma (LCNEC). We hereby investigated the expressions of TrkB and its ligand 
      brain-derived neurotrophic factor (BDNF) in clinical specimens and their 
      influences on phenotypes of invasiveness and tumorigenicity for LCNEC. The 
      expressions of TrkB and BDNF analyzed by immunohistochemistry for patients 
      samples with lung cancer (n=104) were significantly higher in neuroendocrine 
      tumor (NET) compared with non-NET. In particular, LCNEC, a subtype of NET, 
      exhibited significantly higher TrkB and BDNF expressions than another NET type: 
      small cell lung cancer (SCLC), and a significant correlation between TrkB and 
      BDNF expressions was noted in LCNEC but not in SCLC. In vitro assay, exogenous 
      BDNF addition enhanced the invasion into matrigels of LCNEC cells, whereas 
      inhibition of TrkB or BDNF suppressed matrix metalloproteinase-2 and -9 
      activities and the invasiveness. Exogenous BDNF also increased anchor-independent 
      colony formation on soft agar gels for LCNEC, while inhibition of TrkB or BDNF 
      suppressed the anchorage-independency. In vivo experiments, implanted LCNEC cells 
      pretreated with TrkB-siRNA developed no subcutaneous tumor in all six nude mice, 
      although those with control-siRNA formed tumors in four of six nude mice. In 
      conclusion, BDNF/TrkB signal is involved in malignant progression of invasiveness 
      and tumorigenicity for LCNEC, and may be a potential target for LCNEC without 
      standard therapy.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Odate, Seiichi
AU  - Odate S
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Nakamura, Katsuya
AU  - Nakamura K
FAU - Onishi, Hideya
AU  - Onishi H
FAU - Kojima, Masayuki
AU  - Kojima M
FAU - Uchiyama, Akihiko
AU  - Uchiyama A
FAU - Nakano, Kenji
AU  - Nakano K
FAU - Kato, Masato
AU  - Kato M
FAU - Tanaka, Masao
AU  - Tanaka M
FAU - Katano, Mitsuo
AU  - Katano M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130109
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Carcinoma, Large Cell/*metabolism/pathology/therapy
MH  - Carcinoma, Neuroendocrine/*metabolism/pathology/therapy
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*metabolism/pathology/therapy
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Targeted Therapy
MH  - Neoplasm Invasiveness
MH  - Neoplasm Transplantation
MH  - RNA, Small Interfering/genetics
MH  - Receptor, trkB/genetics/*metabolism
MH  - Signal Transduction
MH  - Tumor Stem Cell Assay
EDAT- 2013/01/15 06:00
MHDA- 2013/07/20 06:00
CRDT- 2013/01/15 06:00
PHST- 2012/08/28 00:00 [received]
PHST- 2012/11/29 00:00 [revised]
PHST- 2012/12/01 00:00 [accepted]
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
AID - S0169-5002(12)00649-6 [pii]
AID - 10.1016/j.lungcan.2012.12.004 [doi]
PST - ppublish
SO  - Lung Cancer. 2013 Mar;79(3):205-14. doi: 10.1016/j.lungcan.2012.12.004. Epub 2013 
      Jan 9.