TNFα promotes oral cancer growth, pain, and Schwann cell activation

Abstract Oral cancer is very painful and impairs a patient’s ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair....

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Autores principales:	Elizabeth Salvo, Nguyen H. Tu, Nicole N. Scheff, Zinaida A. Dubeykovskaya, Shruti A. Chavan, Bradley E. Aouizerat, Yi Ye
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82fcadd287374c4b845bc72d2e93228b
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spelling	oai:doaj.org-article:82fcadd287374c4b845bc72d2e93228b2021-12-02T13:51:15ZTNFα promotes oral cancer growth, pain, and Schwann cell activation10.1038/s41598-021-81500-42045-2322https://doaj.org/article/82fcadd287374c4b845bc72d2e93228b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81500-4https://doaj.org/toc/2045-2322Abstract Oral cancer is very painful and impairs a patient’s ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNFα activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNFα is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNFα reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNFα alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNFα. Cancer- or TNFα-activated Schwann cells release pro-nociceptive mediators such as TNFα and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNFα. Our study suggests that TNFα promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNFα or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.Elizabeth SalvoNguyen H. TuNicole N. ScheffZinaida A. DubeykovskayaShruti A. ChavanBradley E. AouizeratYi YeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth Salvo Nguyen H. Tu Nicole N. Scheff Zinaida A. Dubeykovskaya Shruti A. Chavan Bradley E. Aouizerat Yi Ye TNFα promotes oral cancer growth, pain, and Schwann cell activation
description	Abstract Oral cancer is very painful and impairs a patient’s ability to eat, talk, and drink. Mediators secreted from oral cancer can excite and sensitize sensory neurons inducing pain. Cancer mediators can also activate Schwann cells, the peripheral glia that regulates neuronal function and repair. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNFα activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNFα is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNFα reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNFα alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNFα. Cancer- or TNFα-activated Schwann cells release pro-nociceptive mediators such as TNFα and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNFα. Our study suggests that TNFα promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNFα or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.
format	article
author	Elizabeth Salvo Nguyen H. Tu Nicole N. Scheff Zinaida A. Dubeykovskaya Shruti A. Chavan Bradley E. Aouizerat Yi Ye
author_facet	Elizabeth Salvo Nguyen H. Tu Nicole N. Scheff Zinaida A. Dubeykovskaya Shruti A. Chavan Bradley E. Aouizerat Yi Ye
author_sort	Elizabeth Salvo
title	TNFα promotes oral cancer growth, pain, and Schwann cell activation
title_short	TNFα promotes oral cancer growth, pain, and Schwann cell activation
title_full	TNFα promotes oral cancer growth, pain, and Schwann cell activation
title_fullStr	TNFα promotes oral cancer growth, pain, and Schwann cell activation
title_full_unstemmed	TNFα promotes oral cancer growth, pain, and Schwann cell activation
title_sort	tnfα promotes oral cancer growth, pain, and schwann cell activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/82fcadd287374c4b845bc72d2e93228b
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TNFα promotes oral cancer growth, pain, and Schwann cell activation

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