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

IF 28.1 1区 生物学 Q1 CELL BIOLOGY Cell Research Pub Date : 2024-03-11 DOI:10.1038/s41422-024-00946-z
Qun Xu, Ying Cao, Fanni Kong, Jiaqi Liu, Xin Chen, Yifei Zhao, Chin-Hui Lai, Xin Zhou, Hao Hu, Wei Fu, Jian Chen, Jing Yang
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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.

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多种癌细胞类型释放 LIF 和 Gal3,劫持神经信号。
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。在这项研究中,我们报告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,我们发现白血病抑制因子(LIF)和galectin-3(Gal3)是这些癌细胞类型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中的血浆水平都有所升高。我们进一步证明,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,并强烈抑制肿瘤生长。此外,消减外周交感神经的作用同样可以恢复抗肿瘤免疫力。这些结果阐明了多种癌细胞类型劫持神经系统以促进肿瘤进展的一种新的共享机制。
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来源期刊
Cell Research
Cell Research 生物-细胞生物学
CiteScore
53.90
自引率
0.70%
发文量
2420
审稿时长
2.3 months
期刊介绍: Cell Research (CR) is an international journal published by Springer Nature in partnership with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). It focuses on publishing original research articles and reviews in various areas of life sciences, particularly those related to molecular and cell biology. The journal covers a broad range of topics including cell growth, differentiation, and apoptosis; signal transduction; stem cell biology and development; chromatin, epigenetics, and transcription; RNA biology; structural and molecular biology; cancer biology and metabolism; immunity and molecular pathogenesis; molecular and cellular neuroscience; plant molecular and cell biology; and omics, system biology, and synthetic biology. CR is recognized as China's best international journal in life sciences and is part of Springer Nature's prestigious family of Molecular Cell Biology journals.
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