PMID- 29748024
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20220410
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 120
DP  - 2018 Jun
TI  - Expression of brain-derived neurotrophic factor and its receptor TrkB is 
      associated with poor prognosis and a malignant phenotype in small cell lung 
      cancer.
PG  - 98-107
LID - S0169-5002(18)30321-0 [pii]
LID - 10.1016/j.lungcan.2018.04.005 [doi]
AB  - OBJECTIVES: TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and 
      is highly expressed in various cancers, with BDNF-TrkB signaling having been 
      implicated in tumor progression and metastasis. The role of the BDNF-TrkB system 
      in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, 
      however. We examined BDNF and TrkB expression in SCLC patients as well as the 
      function of BDNF-TrkB signaling in SCLC cell lines. MATERIALS AND METHODS: BDNF 
      and TrkB expression in tumor specimens of 58 SCLC patients and 20 non-small cell 
      lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored 
      on the basis of the distribution and intensity of staining. TrkB-overexpressing 
      SCLC (SBC5(TrkB)) cells were established by retrovirus transduction and were 
      examined for the effects of BDNF on intracellular signaling, cell proliferation, 
      and cell migration in vitro. RESULTS: The staining score for TrkB in NSCLC and 
      SCLC specimens was 2.80 +/- 0.19 and 3.60 +/- 0.15, respectively, whereas that for 
      BDNF was 1.95 +/- 0.32 and 2.76 +/- 0.14, respectively. High levels of both TrkB and 
      BDNF expression in SCLC tumors were significantly associated with poor overall 
      survival in multivariate analysis (hazard ratio = 1.821, P = 0.036). BDNF 
      activated AKT and ERK signaling pathways in and promoted the migration of 
      SBC5(TrkB) cells, and these effects were attenuated by the pan-Trk inhibitor 
      GNF-5837. GNF-5837 also inhibited the proliferation of SBC5(TrkB) cells in the 
      presence of BDNF. CONCLUSION: Coexpression of BDNF and TrkB was associated with 
      poor prognosis in SCLC patients, and BDNF promoted the migration of 
      TrkB-overexpressing SCLC cells. TrkB is thus a potential therapeutic target for 
      SCLC.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Kimura, Shinichi
AU  - Kimura S
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Harada, Taishi
AU  - Harada T
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan; Department of Respiratory Medicine, 
      Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. 
      Electronic address: harada-t@kokyu.med.kyushu-u.ac.jp.
FAU - Ijichi, Kayo
AU  - Ijichi K
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Tanaka, Kentaro
AU  - Tanaka K
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Liu, Renpeng
AU  - Liu R
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Shibahara, Daisuke
AU  - Shibahara D
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Kawano, Yuko
AU  - Kawano Y
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Otsubo, Kohei
AU  - Otsubo K
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Yoneshima, Yasuto
AU  - Yoneshima Y
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Iwama, Eiji
AU  - Iwama E
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Nakanishi, Yoichi
AU  - Nakanishi Y
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
FAU - Okamoto, Isamu
AU  - Okamoto I
AD  - Research Institute for Diseases of the Chest, Graduate School of Medical 
      Sciences, Kyushu University, Fukuoka, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180405
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Aged
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*diagnosis/metabolism/pathology
MH  - Male
MH  - Phenotype
MH  - Prognosis
MH  - Receptor, trkB/*metabolism
MH  - Signal Transduction
MH  - Small Cell Lung Carcinoma/*diagnosis/metabolism/pathology
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - NTRK2 gene
OT  - Prognosis
OT  - Small cell lung cancer (SCLC)
OT  - TrkB
EDAT- 2018/05/12 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/05/12 06:00
PHST- 2018/01/24 00:00 [received]
PHST- 2018/04/02 00:00 [revised]
PHST- 2018/04/04 00:00 [accepted]
PHST- 2018/05/12 06:00 [entrez]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
AID - S0169-5002(18)30321-0 [pii]
AID - 10.1016/j.lungcan.2018.04.005 [doi]
PST - ppublish
SO  - Lung Cancer. 2018 Jun;120:98-107. doi: 10.1016/j.lungcan.2018.04.005. Epub 2018 
      Apr 5.