Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice
Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice
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DOI：
10.1016/j.neulet.2016.08.060
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发表时间：
2016-10-06
影响因子：
2.5
通讯作者：
Kawahara, Kohichi
中科院分区：
文献类型：
--
作者：
Maeda, Takehiko;Yamada, Daisuke;Kawahara, Kohichi
癌症引起的骨痛（CIBP）是最常见的癌症引起的疼痛，目前的标准治疗方法无法充分控制。虽然CIBP的病因仍有待充分阐明，但越来越多的证据表明CIBP是独特复杂的。我们测试了脑信号蛋白3A（Sema 3A）信号是否参与小鼠CIBP的发展。用于CIBP的小鼠模型-用刘易斯肺癌（LLC）细胞接种的小鼠，注射到股骨髓内空间中-显示同侧后肢的承重进行性下降。LLC细胞接种导致Sema 3A mRNA表达随着时间的推移逐渐增加，并且同侧股骨中Sema 3A免疫反应细胞的数量增加。为了确定Sema 3A在CIBP发展中的作用，我们采用慢病毒表达系统来建立稳定的LLC细胞系，该细胞系表达用于对照组（LLC/scramble）的乱序shRNA和用于功能丧失组（LLC/shSema 3A）的针对Sema 3A mRNA的shRNA。与接种LLC/scramble的小鼠相比，接种LLC/shSema 3A并未导致股骨中接种细胞的Sema 3A mRNA表达上调和增殖。接种LLC/shSema 3A而非LLC/scramble的小鼠显示出同侧后爪承重显著下降的减弱。我们的研究结果表明，Sema 3A作为一个潜在的治疗CIBP的目标。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Cancer-induced bone pain (CIBP) is the most common pain arising from cancer and is inadequately managed with current standard therapeutics. While the etiology of CIBP remains to be fully elucidated, increasing evidence suggests that CIBP is uniquely complex. We tested whether semaphorin 3A (Sema3A) signals were involved in the development of CIBP in mice. The mouse model employed for CIBP - mice inoculated with Lewis lung carcinoma (LLC) cells injected into the femur intramedullary space - showed progressive decline in the weight bearing of the ipsilateral hind limb. The LLC cell inoculation resulted in a progressive increase in Sema3A mRNA expression over time and an increase in the number of Sema3A-immunoreactive cells in the ipsilateral femur. To define the role of Sema3A in development of CIBP, we employed a lentiviral expression system to establish a stable LLC cell line expressing scrambled shRNA for the control group (LLC/scramble) and shRNAs directed against Sema3A mRNA for the loss-of-function group (LLC/shSema3A). Inoculation of LLC/shSema3A did not cause upregulation of Sema3A mRNA expression and proliferation of the inoculated cells in the femur compared to that in mice inoculated with LLC/scramble. Mice inoculated with LLC/shSema3A, but not LLC/scramble, showed an attenuation of the significant decline in the weight bearing of the ipsilateral hind paw. Our findings indicate that Sema3A serves as a potential therapeutic target for CIBP. (C) 2016 Elsevier Ireland Ltd. All rights reserved.