Inhibition of CDC42 reduces macrophage recruitment and suppresses lung tumorigenesis in vivo

癌变 刘易斯肺癌 基因敲除 CDC42型 癌症研究 生物 小发夹RNA 趋化因子 转移 巨噬细胞 体内 肿瘤微环境 肺癌 免疫学
作者
Bo Zhang,Jian Zhang,Lilong Xia,Jing Luo,Lei Zhang,Yanhui Xu,Xinhai Zhu,Guoping Chen
出处
期刊:Journal of Receptors and Signal Transduction [Taylor & Francis]
被引量:4
标识
DOI:10.1080/10799893.2020.1828916
摘要

Cell division control (CDC) 42 has been involved in the regulation of diverse cancers. Macrophage recruitment plays an important role in the pathogenesis and development of tumor. However, it remains unclear whether CDC42 contributes to macrophage recruitment and lung tumorigenesis in vivo.Small interference RNA (siRNA) was used to knock down CDC42 in the Lewis lung carcinoma (LLC)1. The invasion capability of CDC42 knockdown LLC1 cells was evaluated. LLC1 cells with CDC42 targeted small hairpin RNA (shRNA) were inoculated into C57BL/6 mice to establish the tumor-bearing animal model Tumor size and metastasis related proteins were measured. In addition, the invasion of macrophages in the tumor site as well as macrophage chemokine were also determined in the model.The capacity of invasion and metastasis of LLC1 cells significantly decreased when CDC42 was knocked down. When inoculated with CDC42 knockdown LLC1 cells in vivo, the tumor size and metastasis related proteins levels both decreased. The invasion capacity of macrophages and the associated macrophage chemokine were also significantly down-regulated.Our data suggest that the inhibition of CDC42 expression in lung cancer cells can significantly prevent the pathogenesis and development of tumor in an allograft tumor model in vivo, which might provide a novel therapeutic target and potential strategy for lung cancer treatment in the future.
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