High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer

Tomoya Nakamura, Tatsuo Okui, Kazuaki Hasegawa, Shoji Ryumon, Soichiro Ibaragi, Kisho Ono, Yuki Kunisada, Kyoichi Obata, Masanori Masui, Tsuyoshi Shimo, Akira Sasaki

Research output: Contribution to journalArticlepeer-review

Abstract

Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC-BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC-BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC-BP and the pERK1/2 expression in DRG. It was also observed that HNC-derived HMGB1 increased the expression of the acid-sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC-BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC-BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons.

Original languageEnglish
Pages (from-to)2547-2558
Number of pages12
JournalOncology reports
Volume44
Issue number6
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Bone pain
  • HMGB1
  • Head and neck cancer
  • RAGE
  • Sensory neuron

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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