HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain
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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. 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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain
- Date Crossref
- 07/09/2023
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Michigan State University Department of Physiology pays non établi dans la noticeUniversité ou école supérieure
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Sanford Research pays non établi dans la noticeStructure de recherche
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Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article pays non établi dans la noticeInstitution
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Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com) pays non établi dans la noticeInstitution
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College of Osteopathic Medicine pays non établi dans la noticeUniversité ou école supérieure
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Cancer Biology and Immunotherapies Group pays non établi dans la noticeInstitution
Department of Physiology — Michigan State University, Sanford Research et Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.