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

作者：Morisawa Ayaka; Okui Tatsuo^*; Shimo Tsuyoshi; Ibaragi Soichiro; Okusha Yuka; Ono Mitsuaki; Thi Thu Ha Nguyen; Hassan Nur Mohammad Monsur; Sasaki Akira

来源：International Journal of Oncology, 2018, 52(3): 989-999.

DOI：10.3892/ijo.2018.4242

• copper
• head and neck squamous cell carcinoma
• bone invasion
• osteoclastogenesis

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-B 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.

• 出版日期2018-3