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bioRxiv · 10.1101/2022.09.06.506411

Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain

Inyang, K. E.·Evans, C. M.·Heussner, M.·Petroff, M.·Reimers, M.·Vermer, P. D.·Tykocki, N.·Folger, J. K.·Laumet, G.
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Abstract

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 naive 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. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/506411v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@2a13a2org.highwire.dtl.DTLVardef@6f305dorg.highwire.dtl.DTLVardef@1d0417corg.highwire.dtl.DTLVardef@17b36df_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Inyang, K. E., Evans, C. M., Heussner, M., Petroff, M., Reimers, M., Vermer, P. D., Tykocki, N., Folger, J. K., Laumet, G.. 2022-09-08. Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain. https://doi.org/10.1101/2022.09.06.506411

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