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 Okusha, Mitsuaki Ono, Thi Thu Ha Nguyen, Nur Mohammad Monsur Hassan, Akira Sasaki

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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 2018

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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