Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan.
Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan.
Int J Oncol. 2018 Mar;52(3):989-999. doi: 10.3892/ijo.2018.4242. Epub 2018 Jan 10.
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.
头颈部鳞状细胞癌（HNSCC）在临床上是一个重大的挑战，其中一种导致面部骨骼侵袭的机制是通过破骨细胞的激活。铜已被证明在骨骼重塑中发挥关键作用。然而，铜在癌症相关的骨破坏中的作用目前尚不清楚。赖氨酰氧化酶（LOX）是一种依赖铜的酶，可促进破骨细胞的生成。在本研究中，我们通过体外和体内实验研究了铜螯合剂四硫钼酸铵（TM）对具有骨侵袭的 HNSCC 的影响。我们证明 TM 可阻断 HNSCC 细胞的增殖，抑制 LOX 的激活并降低成骨细胞和骨细胞中核因子-κB 配体受体激活剂（RANKL）的表达，从而抑制骨破坏。这些发现表明铜可能是治疗与骨破坏相关的 HNSCC 的一个潜在靶点。
