Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma

Ayaka Morisawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Yuka Okusya, Mitsuaki Ono, Thi Thu Ha Nguyen, Nur Mohammad Monsur Hassan, Akira Sasaki

Research output: Contribution to journalArticle

Abstract

Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

Original languageEnglish
Pages (from-to)989-999
Number of pages11
JournalInternational Journal of Oncology
Volume52
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Osteogenesis
Copper
Squamous Cell Carcinoma
Neck
Head
Protein-Lysine 6-Oxidase
Bone and Bones
Facial Bones
Osteocytes
Bone Neoplasms
Osteoclasts
Cytoplasmic and Nuclear Receptors
Chelating Agents
Osteoblasts
tetrathiomolybdate
Cetuximab
Ligands
Enzymes
Carcinoma, squamous cell of head and neck

Keywords

  • Bone invasion
  • Copper
  • Head and neck squamous cell carcinoma
  • Osteoclastogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. / Morisawa, Ayaka; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Okusya, Yuka; Ono, Mitsuaki; Nguyen, Thi Thu Ha; Hassan, Nur Mohammad Monsur; Sasaki, Akira.

In: International Journal of Oncology, Vol. 52, No. 3, 01.03.2018, p. 989-999.

Research output: Contribution to journalArticle

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