TNF? 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. The contribution of Schwann cells to oral cancer pain is unclear. We hypothesize that the oral cancer mediator TNF? activates Schwann cells, which further promotes cancer progression and pain. We demonstrate that TNF? is overexpressed in human oral cancer tissues and correlates with increased self-reported pain in patients. Antagonizing TNF? reduces oral cancer proliferation, cytokine production, and nociception in mice with oral cancer. Oral cancer or TNF? alone increases Schwann cell activation (measured by Schwann cell proliferation, migration, and activation markers), which can be inhibited by neutralizing TNF?. Cancer- or TNF?-activated Schwann cells release pro-nociceptive mediators such as TNF? and nerve growth factor (NGF). Activated Schwann cells induce nociceptive behaviors in mice, which is alleviated by blocking TNF?. Our study suggests that TNF? promotes cancer proliferation, progression, and nociception at least partially by activating Schwann cells. Inhibiting TNF? or Schwann cell activation might serve as therapeutic approaches for the treatment of oral cancer and associated pain.

SUBMITTER: Salvo E 

PROVIDER: S-EPMC7815837 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature