Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
Br J Cancer. 2013 Jan 15;108(1):121-30. doi: 10.1038/bjc.2012.499. Epub 2012 Nov 22.
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.
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.
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.
The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.
脑源性神经营养因子（BDNF）是神经生长因子家族的一员，已知其能激活高亲和力原肌球蛋白相关受体激酶 B（TrkB）。本研究旨在阐明 BDNF/TrkB 通路在胃癌中的临床和生物学意义。
我们通过实时逆转录 PCR 和免疫组织化学分析了胃癌样本中的 BDNF 和 TrkB 表达。为了研究 BDNF/TrkB 轴的生物学作用，我们使用重组人 BDNF（rhBDNF）和 Trk 拮抗剂 K252a 进行了体外和体内分析。
与肿瘤核心和相邻正常黏膜相比，原发肿瘤侵袭前沿的 BDNF 表达明显升高。侵袭前沿 BDNF 表达的增加与反映疾病进展和预后不良的因素显著相关。BDNF/TrkB 轴的表达增加与不良预后显著相关。胃癌细胞表达 BDNF，rhBDNF 的给药促进了增殖、迁移、侵袭和对失巢凋亡的抑制。这些作用通常被 K252a 抑制。在体内实验中，注射到裸鼠体内的 BDNF(+)/TrkB(+)胃癌细胞建立了腹膜播散，而 K252a 则抑制了肿瘤生长。
BDNF/TrkB 通路可能深度参与胃癌的疾病进展。
