TY - JOUR
T1 - Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer
AU - Okugawa, Y.
AU - Tanaka, K.
AU - Inoue, Y.
AU - Kawamura, M.
AU - Kawamoto, A.
AU - Hiro, J.
AU - Saigusa, S.
AU - Toiyama, Y.
AU - Ohi, M.
AU - Uchida, K.
AU - Mohri, Y.
AU - Kusunoki, M.
N1 - Funding Information:
We thank Motoko Ueeda and Chihiro Hibi for providing excellent technical assistance. This work was supported in part by a Grant in Aid for Scientific Research (B: 23791525) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
PY - 2013/1/15
Y1 - 2013/1/15
N2 - Background:Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer.Methods:We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis.Results:The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth.Conclusion:The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.
AB - Background:Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer.Methods:We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis.Results:The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth.Conclusion:The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.
KW - Brain-derived neurotrophic factor
KW - anoikis resistance
KW - gastric cancer
KW - tropomyosin-related kinase B
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U2 - 10.1038/bjc.2012.499
DO - 10.1038/bjc.2012.499
M3 - Article
C2 - 23175149
AN - SCOPUS:84872602476
SN - 0007-0920
VL - 108
SP - 121
EP - 130
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 1
ER -
