{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Inyang KE"],"funding":["National Institute of Neurological Disorders and Stroke","NIDCR NIH HHS","NINDS NIH HHS","National Institute of Dental and Craniofacial Research","Rita Allen Foundation"],"pagination":["608-620"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10915104"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["165(3)"],"pubmed_abstract":["<h4>Abstract</h4>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. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown. 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 that is prevented by QX-314 treatment and in Trpv1-/- mice. Cancer-sEVs triggered calcium influx in nociceptors, and inhibition or ablation of nociceptors protects 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. In summary, our work reveals that HPV+ head and neck squamous cell carcinoma-derived sEVs alter TRPV1+ neurons by promoting nascent translation to mediate cancer pain and identified several promising therapeutic targets to interfere with this pathway."],"journal":["Pain"],"pubmed_title":["HPV+ head and neck cancer-derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain."],"pmcid":["PMC10915104"],"funding_grant_id":["R01DE032712","R01 NS121259","R01 DE032712","R01NS121259","2020"],"pubmed_authors":["Folger JK","Heussner M","Petroff M","Reimers M","Vermeer PD","Tykocki N","Evans CM","Inyang KE","Laumet G"],"additional_accession":[]},"is_claimable":false,"name":"HPV+ head and neck cancer-derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain.","description":"<h4>Abstract</h4>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. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown. 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 that is prevented by QX-314 treatment and in Trpv1-/- mice. Cancer-sEVs triggered calcium influx in nociceptors, and inhibition or ablation of nociceptors protects 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. In summary, our work reveals that HPV+ head and neck squamous cell carcinoma-derived sEVs alter TRPV1+ neurons by promoting nascent translation to mediate cancer pain and identified several promising therapeutic targets to interfere with this pathway.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-01T11:13:40.338Z","creation":"2025-06-26T03:06:04.661Z"},"accession":"S-EPMC10915104","cross_references":{"pubmed":["37678566"],"doi":["10.1097/j.pain.0000000000003045"]}}