Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma

Kazuaki Hasegawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Hotaka Kawai, Shoji Ryumon, Koji Kishimoto, Yuka Okusya, Nur Mohammad Monsur Hassan, Akira Sasaki

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number11
DOIs
Publication statusPublished - Oct 25 2018

Fingerprint

Monocarboxylic Acid Transporters
transporter
lactates
pain
bones
Bone
cancer
Bone and Bones
Pain
Spinal Ganglia
Neurons
nerves
SAS
neurons
Small Interfering RNA
mice
Facial Bones
bone marrow
Carcinoma, squamous cell of head and neck
Epithelial Cells

Keywords

  • bone pain
  • head and neck squamous cell carcinoma
  • monocarboxylate transporter 4

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma. / Hasegawa, Kazuaki; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Kawai, Hotaka; Ryumon, Shoji; Kishimoto, Koji; Okusya, Yuka; Monsur Hassan, Nur Mohammad; Sasaki, Akira.

In: International Journal of Molecular Sciences, Vol. 19, No. 11, 25.10.2018.

Research output: Contribution to journalArticle

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