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.

中文翻译：

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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


迷走神经与包括小细胞肺癌 （SCLC） 在内的多个组织中的肿瘤发生有关。然而，交感神经元在 SCLC 发展中的作用仍然未知。在这里，我们在 SCLC 小鼠模型中观察到局部交感神经化学去神经支配后肿瘤生长显着减少。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。ADRB2 的基因缺失或药理学抑制导致肿瘤生长减少和生存率提高。此外，阻断 ADRB2 还减少了人 SCLC 类器官和异种移植物的生长。进一步研究表明，ADRB2 通过激活蛋白激酶 A （PKA） 信号传导促进癌细胞扩增。一致地，抑制 PKA 也降低了 SCLC 细胞的生长。这些发现为交感神经元在 SCLC 发展中的作用提供了初步见解，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。