Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.
Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.
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DOI：
10.1038/bjc.2012.499
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发表时间：
2013-01-15
影响因子：
8.8
通讯作者：
Kusunoki, M.
中科院分区：
文献类型：
--
作者：
Okugawa, Y.;Tanaka, K.;Inoue, Y.;Kawamura, M.;Kawamoto, A.;Hiro, J.;Saigusa, S.;Toiyama, Y.;Ohi, M.;Uchida, K.;Mohri, Y.;Kusunoki, M.
脑源性中性粒细胞因子 (BDNF) 是中性粒细胞家族的成员，已知可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 BDNF 和 TrkB 的表达。为了研究 BDNF/TrkB 轴的生物学作用，使用重组人 BDNF (rhBDNF) 和 Trk 拮抗剂 K252a 进行体外和体内分析。原发肿瘤浸润前沿的 BDNF 表达较肿瘤核心及邻近正常粘膜显着升高。侵袭前沿的 BDNF 表达增加与反映疾病进展和不良预后的因素显着相关。 BDNF/TrkB 轴共表达的增加与不良预后显着相关。胃癌细胞表达BDNF，给予rhBDNF可促进增殖、迁移、侵袭和失巢凋亡的抑制。这些作用通常被 K252a 抑制。在体内试验中，注射到裸鼠体内的 BDNF(+)/TrkB(+) 胃癌细胞建立了腹膜播散，而 K252a 抑制了肿瘤生长。 BDNF/TrkB 通路可能深入参与胃癌疾病进展。
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.
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影响因子：
10.3
作者：
Asgharzadeh, Shahab;Pique-Regi, Roger;Seeger, Robert C.
通讯作者：
Seeger, Robert C.
影响因子：
6.2
作者：
Li Z;Oh DY;Nakamura K;Thiele CJ
通讯作者：
Thiele CJ
影响因子：
5.3
作者：
NAKAGAWARA, A;AZAR, CG;BRODEUR, GM
通讯作者：
BRODEUR, GM
影响因子：
4.5
作者：
Cianchi, F.;Cuzzocrea, S.;Masini, E.
通讯作者：
Masini, E.
影响因子：
9.2
作者：
Moghaddam, Samar Masoumi;Amini, Afshin;Morris, David L.;Pourgholami, Mohammad H.
通讯作者：
Pourgholami, Mohammad H.