Functional Neuronal Circuits Promote Disease Progression in Cancer

Authors

Anthony C Restaino
Austin Walz
Samuel J Vermeer
Jeffrey Barr
Attila Kovács
Robin R Fettig
Daniel W Vermeer
Hunter Reavis
Caitlin S Williamson
Christopher T Lucido
Tuany Eichwald
Dalia K Omran
Euihye Jung
Lauren E Schwartz
Maria Bell
DesiRae M Muirhead
Jody E Hooper
William C Spanos
Ronny Drapkin
Sebastien Talbot
Paola D Vermeer

Publication Date

5-10-2023

Journal

Science Advances

Abstract

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.

Keywords

Animals, Mice, Disease Models, Animal, Humans, Breast Neoplasms, Substance P, Cell Line, Tumor, Squamous Cell Carcinoma of Head and Neck, Ovarian Neoplasms, Neurons, Mice, Inbred C57BL, Specific Pathogen-Free Organisms, Ovary, Human Papillomavirus Viruses, Survival Analysis

Comments

Supplementary Materials

PMID: 37163587