RT Journal Article
SR Electronic
T1 Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.06.506411
DO 10.1101/2022.09.06.506411
A1 Kufreobong E. Inyang
A1 Christine M. Evans
A1 Matthew Heussner
A1 Margaret Petroff
A1 Mark Reimers
A1 Paola D. Vermeer
A1 Nathan Tykocki
A1 Joseph K. Folger
A1 Geoffroy Laumet
YR 2022
UL http://biorxiv.org/content/early/2022/09/08/2022.09.06.506411.abstract
AB Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain, because of our lack of mechanistic understanding. Cancer-derived small extracellular vesicles (Cancer-sEVs) are well- positioned to function as mediators of communication between cancer cells and neurons. Inhibition of Cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified Cancer-sEVs is sufficient to induce pain hypersensitivity in naïve mice. Cancer-sEVs triggered calcium influx in nociceptors and inhibition or ablation of nociceptors protect against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human Cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by Cancer-sEVs was validated in our mouse model and its inhibition alleviated cancer pain in mice. These findings define a role of Cancer-sEVs in cancer pain and identify several druggable targets.Competing Interest StatementThe authors have declared no competing interest.