Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer.
Brain-derived neurotrophic factor (BDNF)-induced tropomyosin-related kinase B (Trk B) signaling is a potential therapeutic target for peritoneal carcinomatosis arising from colorectal cancer.
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DOI：
10.1371/journal.pone.0096410
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kusunoki M
中科院分区：
文献类型：
--
作者：
Tanaka K;Okugawa Y;Toiyama Y;Inoue Y;Saigusa S;Kawamura M;Araki T;Uchida K;Mohri Y;Kusunoki M
原肌球蛋白相关受体激酶B（Trk B）信号在脑源性神经营养因子（BDNF）配体的刺激下促进肿瘤的进展，并与多种恶性肿瘤的不良预后相关。我们试图研究BDNF/TrkB在结直肠癌（CRC）组织中表达的临床相关性，其对CRC患者的预后价值，以及其在体外和体内的治疗潜力。223例CRC患者标本用于测定BDNF和TrkB mRNA水平。免疫组化法检测这些蛋白在原发瘤和转移瘤中的表达。CRC细胞系和重组BDNF和K252 a（选择性药理学泛Trk抑制剂）用于体外细胞活力、迁移、侵袭、失巢凋亡抗性和体内腹膜转移测定。组织BDNF mRNA与肝转移和腹膜转移相关。组织TrkB mRNA表达与淋巴结转移有关。BDNF和TrkB的共同表达与肝转移和腹膜转移有关。BDNF、TrkB及BDNF和TrkB共同表达的患者预后显著不良。BDNF在表达TrkB的CRC细胞系中增加肿瘤细胞活力、迁移、侵袭并抑制失巢凋亡。这些作用被K252 a抑制。与对照小鼠相比，在用共表达BDNF和TrkB的DLD 1注射并随后用K252 a处理的小鼠中，发现腹膜转移结节减少。因此，BDNF/TrkB信号转导可能是治疗结直肠癌引起的腹膜癌转移的潜在靶点。
Tropomyosin-related receptor kinase B (TrkB) signaling, stimulated by brain-derived neurotrophic factor (BDNF) ligand, promotes tumor progression, and is related to the poor prognosis of various malignancies. We sought to examine the clinical relevance of BDNF/TrkB expression in colorectal cancer (CRC) tissues, its prognostic value for CRC patients, and its therapeutic potential in vitro and in vivo. Two hundred and twenty-three CRC patient specimens were used to determine both BDNF and TrkB mRNA levels. The expression of these proteins in their primary and metastatic tumors was investigated by immunohistochemistry. CRC cell lines and recombinant BDNF and K252a (a selective pharmacological pan-Trk inhibitor) were used for in vitro cell viability, migration, invasion, anoikis resistance and in vivo peritoneal metastasis assays. Tissue BDNF mRNA was associated with liver and peritoneal metastasis. Tissue TrkB mRNA was also associated with lymph node metastasis. The co-expression of BDNF and TrkB was associated with liver and peritoneal metastasis. Patients with higher BDNF, TrkB, and co-expression of BDNF and TrkB had a significantly poor prognosis. BDNF increased tumor cell viability, migration, invasion and inhibited anoikis in the TrkB-expressing CRC cell lines. These effects were suppressed by K252a. In mice injected with DLD1 co-expressing BDNF and TrkB, and subsequently treated with K252a, peritoneal metastatic nodules was found to be reduced, as compared with control mice. BDNF/TrkB signaling may thus be a potential target for treating peritoneal carcinomatosis arising from colorectal cancer.
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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：
11.2
作者：
Li Z;Chang Z;Chiao LJ;Kang Y;Xia Q;Zhu C;Fleming JB;Evans DB;Chiao PJ
通讯作者：
Chiao PJ
DOI：
10.1006/bbrc.2001.4296
发表时间：
2001-02-09
影响因子：
3.1
作者：
Haapasalo, A;Koponen, E;Castrén, E
通讯作者：
Castrén, E
DOI：
10.1523/jneurosci.5060-08.2009
发表时间：
2009-01-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Carim-Todd L;Bath KG;Fulgenzi G;Yanpallewar S;Jing D;Barrick CA;Becker J;Buckley H;Dorsey SG;Lee FS;Tessarollo L
通讯作者：
Tessarollo L
影响因子：
9
作者：
Koppe, MJ;Boerman, OC;Bleichrodt, RP
通讯作者：
Bleichrodt, RP