PMID- 23175149 OWN - NLM STAT- MEDLINE DCOM- 20130307 LR - 20211117 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 108 IP - 1 DP - 2013 Jan 15 TI - Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer. PG - 121-30 LID - 10.1038/bjc.2012.499 [doi] 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. FAU - Okugawa, Y AU - Okugawa Y AD - Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu 514-8507, Japan. FAU - Tanaka, K AU - Tanaka K FAU - Inoue, Y AU - Inoue Y FAU - Kawamura, M AU - Kawamura M FAU - Kawamoto, A AU - Kawamoto A FAU - Hiro, J AU - Hiro J FAU - Saigusa, S AU - Saigusa S FAU - Toiyama, Y AU - Toiyama Y FAU - Ohi, M AU - Ohi M FAU - Uchida, K AU - Uchida K FAU - Mohri, Y AU - Mohri Y FAU - Kusunoki, M AU - Kusunoki M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121122 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 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 Proliferation MH - Disease Progression MH - Female MH - Humans MH - Male MH - Prognosis MH - Receptor, trkB/*metabolism MH - Stomach Neoplasms/*metabolism PMC - PMC3553513 EDAT- 2012/11/24 06:00 MHDA- 2013/03/08 06:00 PMCR- 2014/01/15 CRDT- 2012/11/24 06:00 PHST- 2012/11/24 06:00 [entrez] PHST- 2012/11/24 06:00 [pubmed] PHST- 2013/03/08 06:00 [medline] PHST- 2014/01/15 00:00 [pmc-release] AID - bjc2012499 [pii] AID - 10.1038/bjc.2012.499 [doi] PST - ppublish SO - Br J Cancer. 2013 Jan 15;108(1):121-30. doi: 10.1038/bjc.2012.499. Epub 2012 Nov 22.