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

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 Oncol

authors

Morisawa A,Okui T,Shimo T,Ibaragi S,Okusha Y,Ono M,Nguyen TTH,Hassan NMM,Sasaki A

doi

10.3892/ijo.2018.4242

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

989-999

issue

3

eissn

1019-6439

issn

1791-2423

journal_volume

52

pub_type

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