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.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Morisawa A,Okui T,Shimo T,Ibaragi S,Okusha Y,Ono M,Nguyen TTH,Hassan NMM,Sasaki Adoi
10.3892/ijo.2018.4242subject
Has Abstractpub_date
2018-03-01 00:00:00pages
989-999issue
3eissn
1019-6439issn
1791-2423journal_volume
52pub_type
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