Neural activity recorded in breast tumors originates from the sympathetic nervous

The autonomic nervous system (ANS) is a regulator of major pathological events in the tumor microenvironment (TME) of solid carcinomas where the branches of ANS have antagonistic effects on tumor growth and metastasis. Neural activity recorded from breast tumors may be associated with autonomic system function. To test this hypothesis, we performed in vivo chronic electrical recordings from murine mammary tumors of triple negative breast cancers (TNBC) following complete sub-diaphragmatic vagotomy and chemical sympathectomy. In addition to TNBC mammary tumors, we also obtained daily electrical recordings from mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) following chemical sympathectomy. Our results show that tumoral neural activity is partially blocked in vagotomized animals while it is completely absent in the sympathectomized subjects. These studies indicate that neural activity in TNBC and HER2+ tumors is predominantly generated by peripheral nor-adrenergic sympathetic nerves and provide evidence of a strong active link between the brain and tumor through the autonomic nervous system. The results implicate a new and as yet unexplored mechanism to investigate the potential role of the sympathetic nervous system in the regulation of tumor growth and metastasis. To analyze the transcriptomic change in the onset of neural activity, we collected tumors before and at the day of the first peak to extract RNAs.