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

Sep 21, 2026

The nervous system is increasingly recognized as a factor shaping cancer prognosis, and recent evidence suggests cancers can actively engage neural circuitry to promote survival and progression. This article investigates how peripheral cancers communicate with the central nervous system using multiple mouse allograft models. It maps brain activation responses to tumor-bearing states by immunostaining neuronal activity markers across rostrocaudal brain regions. Results identify a shared activation pattern and implicate specific signaling pathways released by cancer cells in hijacking neural signals.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Results

An overlapping pattern of brain responses to multiple types of peripheral cancers

Discussion

[www.nature.com/cr](www.nature.com/cr) Cell [Research](Research www.cell-research.com)[ www.cell-research.com](Research www.cell-research.com) ARTICLE OPEN Multiple cancer cell types release LIF and Gal3 to hijack neural signals Qun Xu1, Ying Cao2, Fanni Kong2, Jiaqi Liu1, Xin Chen3, Yifei Zhao3, Chin-Hui Lai4, Xin Zhou3,5, Hao Hu4, Wei Fu3,5, Jian Chen 6 and 1,2,5,7 ✉ Jing Yang © The Author(s) 2024 INTRODUCTION It has become increasingly recognized that the nervous system can signiﬁcantly inﬂuence cancer prognosis. Indeed, the emerging frontier of cancer neuroscience has garnered research attention in the past years.1–3 For instance, the presence of sympathetic or parasympathetic innervations in prostate tumors correlated with poorer survival of patients.4 Conversely, the incidence of prostate cancer decreased in the male population inﬂicted by spinal cord injuries that conceivably abrogated the efferent sympathetic or parasympathetic actions.5 In the women taking β-adrenergic receptor-antagonizing drugs (i.e., beta blockers) that chronically attenuated sympathetic signaling, the rates of metastasis or mortality became signiﬁcantly lower for breast cancer6,7 or ovary cancer.8 In addition, the use of beta-blockers improved the survival outcomes of non-small-cell lung cancer patients receiving radiotherapy,9 chemotherapy,10 or immunotherapy.11 Therefore, the comprehensive knowledge of cancer neuroscience holds the promise of revealing novel diagnostic or therapeutic strategies against those dreadful human diseases. Clinical observations on the involvement of the body’s nervous system in cancers can be recapitulated in mouse models, which offer valuable mechanistic insights. For example, the local ablation of sympathetic or parasympathetic innervations in the mouse prostate elucidated their disparate roles in tumorigenesis or tumor progression.4 Surgical or pharmacological blockage of neural innervations in the mouse stomach suppressed the Wnt-mediated cell proliferation, thus ameliorating the onset and growth of gastric cancer.12 In addition, the beta-blocker treatment in mice slowed the metastasis of breast cancer by decreasing the inﬁltration of tumor-associated macrophages.13 Furthermore, inhibiting the neurotransmitter glutamate signaling via the Nmethyl-D-aspartate receptor reduced the invasiveness of the mouse pancreatic neuroendocrine tumor or pancreatic ductaladenocarcinoma.14 The complexity of cancer–neural interactions calls for more indepth investigations. Notably, recent studies have begun suggesting that cancer cells proactively engage the nervous system to beneﬁt their survival. For instance, cancer cells in a mouse model of pancreatic ductal adenocarcinoma could release nerve growth factor (NGF), promoting the inﬁltration of sympathetic axons to exaggerate tumor progression.15 Similarly, various human cell lines of prostate cancer, colon cancer, or pancreatic cancer produced the precursor of brain-derived neurotrophic factor (proBDNF), which led to the increase of neural innervations to tumors.16 Moreover, in the mouse allograft models of MC38 colon adenocarcinoma and Pan02 pancreatic ductal adenocarcinoma orthe Apcmin/+ model of intestinal tumors, peripheral cancers could trigger the activation of catecholaminergic neurons in theventrolateral medulla, facilitating tumor growth via an inhibition of CD8+ T cells.17 In addition, the pituitary production of α-melanocyte-stimulating hormone (i.e., α-MSH) occurred in the mouse allograft models of Lewis lung carcinoma (LLC), MC38 colon adenocarcinoma, MCA205 ﬁbrosarcoma, or B16-F10 melanoma, stimulating the generation of myeloid-derived suppressor cells (MDSCs) to dampen antitumor immunity.18 Despite these research advances, pathophysiological mechanisms underlying 1State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China. 2Center for Life Sciences, Academy for Advanced Interdisciplinary Studies,

FAQs

How does the article describe the relationship between the nervous system and cancer prognosis?

It explains that nervous system activity can significantly influence cancer prognosis, motivating research into cancer neuroscience and cancer–neural interactions.

What experimental approach does the study use to examine tumor communication with the brain?

It uses several mouse allograft models with subcutaneous implantation of cancer cell lines, then processes brain tissue for immunostaining of phospho-ribosomal protein S6 as a marker of neuronal activation.

What key finding does the study report about brain responses across different cancers?

It identifies a shared overlapping pattern of brain responses in tumor-bearing mice, including activation in the hypothalamic paraventricular nucleus and other brain regions.

Sep 21, 2026

Uploaded by Ava Thompson