TY - JOUR
T1 - Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma
AU - Morisawa, Ayaka
AU - Okui, Tatsuo
AU - Shimo, Tsuyoshi
AU - Ibaragi, Soichiro
AU - Okusha, Yuka
AU - Ono, Mitsuaki
AU - Nguyen, Thi Thu Ha
AU - Hassan, Nur Mohammad Monsur
AU - Sasaki, Akira
N1 - Includes bibliographical references.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Bone invasion
KW - Copper
KW - Head and neck squamous cell carcinoma
KW - Osteoclastogenesis
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U2 - 10.3892/ijo.2018.4242
DO - 10.3892/ijo.2018.4242
M3 - Article
C2 - 29328370
AN - SCOPUS:85041570641
SN - 1019-6439
VL - 52
SP - 989
EP - 999
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 3
ER -