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Papers of the Week

Papers: 6 May 2023 - 12 May 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology


2023 May 10

Sci Adv




Functional neuronal circuits promote disease progression in cancer.


Restaino AC, Walz A, Vermeer SJ, Barr J, Kovács A, Fettig RR, Vermeer DW, Reavis H, Williamson CS, Lucido CT, Eichwald T, Omran DK, Jung E, Schwartz LE, Bell M, Muirhead DM, Hooper JE, Spanos WC, Drapkin R, Talbot S, Vermeer PD


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.