Details

Autor(en) / Beteiligte

• Xiong, Si-Yi
• Wen, Hui-Zhong
• Dai, Li-Meng
• Lou, Yun-Xiao
• Wang, Zhao-Qun
• Yi, Yi-Lun
• Yan, Xiao-Jing
• Wu, Ya-Ran
• Sun, Wei
• Chen, Peng-Hui
• Yang, Si-Zhe
• Qi, Xiao-Wei
• Zhang, Yi
• Wu, Guang-Yan

Titel

A brain-tumor neural circuit controls breast cancer progression in mice

Ist Teil von

• The Journal of clinical investigation, 2023-12, Vol.133 (24), p.1-18

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.