Sympathetic Neurons Promote Small Cell Lung Cancer Through the Beta-2 Adrenergic Receptor

IF 4 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-11-08 DOI:10.1158/2159-8290.cd-24-0718

Tala FNU, Peiguo Shi, Wanwei Zhang, Sanny S.W. Chung, Christopher B. Damoci, Yinshan Fang, Qi-Yue Chen, Anjali Saqi, Yuefeng Huang, Xuebing Wu, Chao Lu, Dian Yang, Timothy C. Wang, Jianwen Que

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Abstract

The vagal nerve is linked to tumorigenesis in multiple tissues including small cell lung cancer (SCLC). However, the role of sympathetic neuron in SCLC development remains unknown. Here, we observed a significant reduction in tumor growth following chemical denervation of local sympathetic nerves in a mouse model of SCLC. Further study identified that β2-adrenergic receptor (ADRB2) on cancer cells mediated the crosstalk with nerve fibers. Genetic deletion or pharmacological inhibition of ADRB2 led to reduced tumor growth and improved survival. Moreover, blocking ADRB2 also reduced the growth of human SCLC organoids and xenografts. Further studies revealed that ADRB2 promoted cancer cell expansion through activating Protein Kinase A (PKA) signaling. Consistently, inhibition of PKA also reduced the growth of SCLC cells. These findings offer the initial insight into the role played by sympathetic neurons in the development of SCLC and may open a new therapeutic avenue to treat this deadly malignancy.

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交感神经元通过β-2肾上腺素能受体促进小细胞肺癌的发生

迷走神经与包括小细胞肺癌（SCLC）在内的多种组织的肿瘤发生有关。然而，交感神经元在小细胞肺癌发生中的作用仍然未知。在这里，我们观察到，在小鼠 SCLC 模型中对局部交感神经进行化学去神经化后，肿瘤生长明显减少。进一步研究发现，癌细胞上的β2肾上腺素能受体（ADRB2）介导了与神经纤维的串扰。基因缺失或药物抑制ADRB2可减少肿瘤生长，提高生存率。此外，阻断 ADRB2 还能减少人 SCLC 器官组织和异种移植物的生长。进一步的研究发现，ADRB2通过激活蛋白激酶A（PKA）信号促进了癌细胞的扩张。同样，抑制 PKA 也会降低 SCLC 细胞的生长。这些发现让人们初步了解了交感神经元在SCLC发展过程中扮演的角色，并可能为治疗这种致命的恶性肿瘤开辟一条新的治疗途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioconjugate Chemistry Bioconjugate 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.