北京大学Jing Yang研究组近日取得一项新成果。经过不懈努力，他们发现多种类型癌细胞释放的LIF和Gal3会劫持神经信号。该研究于2024年3月11日发表于国际学术期刊《细胞研究》杂志上。

在这项研究中，研究人员建立了多种外周癌症小鼠模型大脑反应的重叠模式，包括下丘脑室旁核的反应。通过多组学筛选，研究人员发现白血病抑制因子（LIF）和galectin-3（Gal3）是这些癌细胞释放的引发脑激活的关键细胞因子。重要的是，这两种细胞因子在不同癌症患者的血浆水平都有所升高。

研究进一步证明，药物或基因阻断癌细胞衍生的LIF或Gal3信号可消除脑部反应，并明显抑制肿瘤生长。此外，消除外周交感神经作用同样可以恢复抗肿瘤免疫。这些结果阐明了多种类型癌细胞劫持神经系统促进肿瘤进展的新共享机制。

据悉，神经信号可对癌症预后产生重大影响。然而，人们对癌细胞如何主动调节神经系统以利于自身生存尚不完全了解。

附：英文原文

Title: Multiple cancer cell types release LIF and Gal3 to hijack neural signals

Author: Xu, Qun, Cao, Ying, Kong, Fanni, Liu, Jiaqi, Chen, Xin, Zhao, Yifei, Lai, Chin-Hui, Zhou, Xin, Hu, Hao, Fu, Wei, Chen, Jian, Yang, Jing

Issue&Volume: 2024-03-11

Abstract: Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by these cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.

DOI: 10.1038/s41422-024-00946-z

Source: https://www.nature.com/articles/s41422-024-00946-z