Chronic neural activity recorded within breast tumors

Grant A Mccallum,Jay Shiralkar,Dominique M Durand,Diana Suciu,Efstathios Karathanasis,Jennifer S Yu,Gil Covarrubias

doi:10.1038/s41598-020-71670-y

Abstract

Nerve fibers are known to reside within malignant tumors and the greater the neuronal density the worse prognosis for the patient. Recent discoveries using tumor bearing animal models have eluded to the autonomic nervous system having a direct effect on tumor growth and metastasis. We report the first direct and chronic in vivo measurements of neural activity within tumors. Using a triple-negative mammary cancer mouse model and chronic neural interface techniques, we have recorded neural activity directly within the tumor mass while the tumor grows and metastasizes. The results indicate that there is a strong connection between the autonomic nervous system and the tumor and could help uncover the mechanisms of tumor growth and metastasis.

Highlights

Nerve fibers are known to reside within malignant tumors and the greater the neuronal density the worse prognosis for the patient
Neurotransmitters were first shown to promote the migration of cancer cells in c ulture[9,10] and a landmark study using genetically engineered mice revealed that sympathetic nervous system signaling through the neurotransmitter norepinephrine, can promote early prostate cancer development, while the parasympathetic branch of the nervous system, signaling through the acetylcholine neurotransmitter promotes a metastatic phenotype
The murine 4T1 model represents a model of triple-negative mammary cancer, which develops metastasis in immunocompetent mice at organs reminiscent of those observed in human patients

Summary

Introduction

Nerve fibers are known to reside within malignant tumors and the greater the neuronal density the worse prognosis for the patient. As mentioned above, increased sympathetic branch activity enhanced metastasis of primary breast cancer Based on these breast cancer studies, increased vagus nerve activity to the brain can transmit information about precancerous cells via tumor-associated proinflammatory cytokines. 10 ms increased sympathetic activity in animal studies showed increased, stress-induced tumor p rogression[20] These studies provide a starting point to understand the autonomic nervous system’s influence on breast cancer progression. None of these studies have reported direct recordings and/or quantified the neural activity within the solid tumors to ascertain whether these neural fibers are active and, if so, what neural signaling patterns are occurring within the solid tumor during its development through metastasis

Methods

Results

Conclusion