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

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

doi:10.3892/or.2020.7788

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

Authors:
- Tomoya Nakamura
- Tatsuo Okui
- Kazuaki Hasegawa
- Shoji Ryumon
- Soichiro Ibaragi
- Kisho Ono
- Yuki Kunisada
- Kyoichi Obata
- Masanori Masui
- Tsuyoshi Shimo
- Akira Sasaki
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Affiliations: Department of Oral and Maxillofacial Surgery and Biopathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama 700‑8525, Japan, Division of Reconstructive Surgery for Oral and Maxillofacial Region, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido 061‑0293, Japan
Published online on: October 2, 2020 https://doi.org/10.3892/or.2020.7788
Pages: 2547-2558
Copyright: © Nakamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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