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

Morisawa, Ayaka; Okui, Tatsuo; Shimo, Tsuyoshi; Ibaragi, Soichiro; Okusha, Yuka; Ono, M.; Nguyen, Tin; Hassan, Nur Mohammad Monsur; Sasaki, Akira

doi:10.3892/ijo.2018.4242

Cited by 14 publications

(19 citation statements)

References 24 publications

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“…Copper is another potential target for the treatment of OSCC associated with bone destruction because copper can play a key role in skeletal remodeling. Ammonium tetrathiomolybdate, copper chelator, blocks the proliferation of OSCC cells, inhibits lysyl oxidase activation and decreases the expression of RANKL in osteoblasts and osteocytes, subsequently suppressing bone destruction 44 .…”

Section: Discussionmentioning

confidence: 99%

“…In a physiological situation bone-resorbing osteoclasts and bone-forming osteoblasts are balanced. Osteoclastogenesis can be activated in several ways, for example: the osteoclast activation controlled by RANK-RANKL-OPG pathway, VEGF or copper [41][42][43][44] .…”

Section: Bone Invasionmentioning

confidence: 99%

“…Morisawa et al investigated the effects of copper on OSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM). It was demonstrated that TM blocks the proliferation of OSCC 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 44 .…”

Section: Copper and Lysyl Oxidasementioning

confidence: 99%

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Prognostic and predictive markers for perineural and bone invasion of oral squamous cell carcinoma

Michálek¹,

Brychtová²,

Pink³

et al. 2019

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One of the most important factors affecting the risk of tumor recurrence and overall prognosis is perineural invasion and bone invasion. Perineural invasion is defined as a tumor spreading and the ability of tumor cells to penetrate around or through the nerve tissue. Perineural invasion can cause the tumor to spread to distant areas from the primary tumor location. One possible explanation for this is the formation of microenvironment in the perineural space which may contain cellular factors that act on both nerve tissue and some types of tumor tissues. Bone invasion by OSCC has major implications for tumor staging, choice of treatment, outcome and quality of life. Oral SCCs invade the mandibular or maxillary bone through an erosive, infiltrative or mixed pattern that correlates with clinical behavior. Bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. Some cytokines (e.g. TNFα and PTHrP) lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression in oral SCC cells and in cancer stromal cells to induce osteoclastogenesis. Oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. A more molecular-based clinical staging and tailor-made therapy would benefit patients with bone invasion by OSCC.

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Section: Discussionmentioning

confidence: 99%

Section: Bone Invasionmentioning

confidence: 99%

Section: Copper and Lysyl Oxidasementioning

confidence: 99%

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Prognostic and predictive markers for perineural and bone invasion of oral squamous cell carcinoma

Michálek¹,

Brychtová²,

Pink³

et al. 2019

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…The monoclonal antibody Cetuximab, which binds specifically to the epidermal growth factor receptor (EGFR) thereby blocking transmission the relative proliferative signaling pathways, is an example of an immunotherapeutic agent. Combination of TM and Cetuximab has been evaluated in a murine model of head and neck squamous cell carcinoma but no statistically significant differences were observed between single and combined treatments [148]. Therefore, further investigations are needed to determine the clinical significance of combining copper chelation and monoclonal antibodies-mediated immunotherapy.…”

Section: Copper Chelation and Monoclonal Antibodies Immunotherapymentioning

confidence: 99%

Current Biomedical Use of Copper Chelation Therapy

Baldari

Rocco

Toietta

2020

IJMS

114

105

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Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

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“…Cancer cells have been demonstrated to secrete significant amounts of growth factors that can promote osteoclastogenesis [ 4 , 5 ]. Protons (H + ) are well known as a pain inducer [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma

Hasegawa

Okui

Shimo

et al. 2018

IJMS

Self Cite

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Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically, as it can invade facial bones and cause bone pain that is undertreated and poorly understood. Here we studied HNSCC bone pain (HNSCC-BP) in an intratibial mouse xenograft model that uses a human HNSCC cell line (SAS cells). These mice develop HNSCC-BP associated with an upregulation of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in the dorsal root ganglia (DRGs) of sensory nerve cell bodies. Our experiments demonstrated that the inhibition of monocarboxylate transporter 4 (MCT4) by short hairpin (shRNA) transduction suppressed the HNSCC-BP, the lactate level in bone marrow, and the pERK1/2 expression in DRG. The sensory nerves also expressed increased levels of the acid-sensing receptor TRPV1. DRG neurons co-cultured with SAS cells showed increased neurite outgrowth, and were inhibited by MCT4 silencing with shRNA. Collectively, our results show that HNSCC induced an acidic bone microenvironment that evokes HNSCC-BP via MCT4 expression.

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

Cited by 14 publications

References 24 publications

Prognostic and predictive markers for perineural and bone invasion of oral squamous cell carcinoma

Prognostic and predictive markers for perineural and bone invasion of oral squamous cell carcinoma

Current Biomedical Use of Copper Chelation Therapy

Lactate Transporter Monocarboxylate Transporter 4 Induces Bone Pain in Head and Neck Squamous Cell Carcinoma

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