当研究人员删除TrkB

sinkevicius kw, et al.

很多时候,癌细胞想要迁移利用的是癌细胞内因(内在机制),sinkevicius解释说:研究原发性肺肿瘤细胞迁移是否可能由bdnf信号驱动,探究是否可以阻断癌细胞与bdnf信号交流,预防癌症细胞迁移?

lung cancer is notorious for its ability to metastasize, but the pathways regulating lung cancer metastasis are largely unknown. an in vitro system designed to discover factors critical for lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase b (trkb; also called ntrk2). knockdown of trkb in human lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. in an autochthonous lung adenocarcinoma model driven by activated oncogenic kras and p53 loss, trkb deficiency significantly reduced metastasis. hypoxia-inducible factor-1 directly regulated trkb expression, and, in turn, trkb activated akt signaling in metastatic lung cancer cells. finally, trkb expression was correlated with metastasis in patient samples, and trkb was detected more often in tumors that did not have kras or epidermal growth factor receptor mutations. these studies demonstrate that trkb is an important therapeutic target in metastatic lung adenocarcinoma.

当sinkevicius取缔,培养中的腺癌细胞迁移显著被抑制,这表明肿瘤细胞使用bdnf信号来为迁移服务

neurotrophin receptor trkb promotes lung adenocarcinoma metastasis.

这个问题导致了他们发现所谓的细胞受体分子--trkb当研究人员删除trkb,细胞迁移再次显著下降而当他们在腺癌老鼠模型中删除trkb,只有17%的小鼠发生转移,与对照组的50%比率相比,转移发生情况大大降低

当腺癌细胞在低氧条件下培养(低氧环境下,肺癌更倾向于转移),trkb尤为丰富缺氧的肿瘤细胞会处于“紧张状态”,可能会积极迁移扩散到别的部位去,sinkevicius认为:trkb正是这些癌细胞迁移扩散的钥匙

波士顿儿童医院kerstin sinkevicius研究员起初有这样的疑问:肺部肿瘤环境中是否存在什么,使得癌细胞得以转移?她从癌症患者淋巴结采样组织样本(淋巴结通常是癌症扩散转移的首个部位),分析癌细胞附近的细胞是否分泌任何可能引诱癌细胞迁移的因子

传统上,癌症转移一直是研究重点但制药公司一般更喜欢寻求能缩小原发肿瘤的药物,而抗转移药物未得到很多投资,因为转移是可变的,转移过程可能需要数年才会发生

一种生长因子让研究人员眼前一亮:癌细胞附近的成熟神经元分泌的脑源性神经营养因子或bdnf会加剧癌细胞迁移,bdnf主要在刺激神经系统发育中发挥作用

然而与先前识别的用于防止转移的靶标相比,trkb可能更容易触及,根据kim所述:这是因为由于trkb抑制剂已经上市,并正在测试用于治疗抑郁症和神经性病症如癫痫

2014年8月16日讯 /生物谷bioon/--9%的肺癌死亡是癌细胞扩散或癌细胞转移到其他器官引起的,现在研究人员已经发现一种潜在新方法,来阻止最常见类型肺腺癌转移

pmc:

pmid:

doi:10.1073/pnas.