Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
March-2018 Volume 52 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2018 Volume 52 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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

  • Authors:
    • Ayaka Morisawa
    • Tatsuo Okui
    • Tsuyoshi Shimo
    • Soichiro Ibaragi
    • Yuka Okusha
    • Mitsuaki Ono
    • Thi Thu Ha Nguyen
    • Nur Mohammad Monsur Hassan
    • Akira Sasaki
  • View Affiliations / Copyright

    Affiliations: 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, Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan, Department of Oral Rehabilitation Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan, School of Dentistry and Health Sciences, Charles Sturt University, Sydney, Orange NSW, Australia
  • Pages: 989-999
    |
    Published online on: January 10, 2018
       https://doi.org/10.3892/ijo.2018.4242
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Brown JS, Lowe D, Kalavrezos N, D'Souza J, Magennis P and Woolgar J: Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma. Head Neck. 24:370–383. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Shaw RJ, Brown JS, Woolgar JA, Lowe D, Rogers SN and Vaughan ED: The influence of the pattern of mandibular invasion on recurrence and survival in oral squamous cell carcinoma. Head Neck. 26:861–869. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Takada H, Ibaragi S, Eguchi T, Okui T, Obata K, Masui M, Morisawa A, Takabatake K, Kawai H, Yoshioka N, et al: Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma. Int J Oncol. 51:625–632. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Spence JA, Suttle NF, Wenham G, El-Gallad T and Bremner I: A sequential study of the skeletal abnormalities which develop in rats given a small dietary supplement of ammonium tetrathiomolybdate. J Comp Pathol. 90:139–153. 1980. View Article : Google Scholar : PubMed/NCBI

5 

Smith BJ, King JB, Lucas EA, Akhter MP, Arjmandi BH and Stoecker BJ: Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats. J Nutr. 132:190–196. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Roberts EA and Schilsky ML; American Association for Study of Liver Diseases (AASLD): Diagnosis and treatment of Wilson disease: An update. Hepatology. 47:2089–2111. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Chan N, Willis A, Kornhauser N, Ward MM, Lee SB, Nackos E, Seo BR, Chuang E, Cigler T, Moore A, et al: Influencing the tumor microenvironment: A phase II study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases. Clin Cancer Res. 23:666–676. 2017. View Article : Google Scholar

8 

Hassouneh B, Islam M, Nagel T, Pan Q, Merajver SD and Teknos TN: Tetrathiomolybdate promotes tumor necrosis and prevents distant metastases by suppressing angiogenesis in head and neck cancer. Mol Cancer Ther. 6:1039–1045. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Bhuvanasundar R, John A, Sulochana KN, Coral K, Deepa PR and Umashankar V: A molecular model of human Lysyl Oxidase (LOX) with optimal copper orientation in the catalytic cavity for induced fit docking studies with potential modulators. Bioinformation. 10:406–412. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Rucker RB, Kosonen T, Clegg MS, Mitchell AE, Rucker BR, Uriu-Hare JY and Keen CL: Copper, lysyl oxidase, and extracellular matrix protein cross-linking. Am J Clin Nutr. 67(Suppl): S996–S1002. 1998. View Article : Google Scholar

11 

Tsukasaki M, Hamada K, Okamoto K, Nagashima K, Terashima A, Komatsu N, Win SJ, Okamura T, Nitta T, Yasuda H, et al: LOX fails to substitute for RANKL in osteoclastogenesis. J Bone Miner Res. 32:434–439. 2017. View Article : Google Scholar

12 

Cox TR, Rumney RMH, Schoof EM, Perryman L, Høye AM, Agrawal A, Bird D, Latif NA, Forrest H, Evans HR, et al: The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 522:106–110. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Reynaud C, Ferreras L, Di Mauro P, Kan C, Croset M, Bonnelye E, Pez F, Thomas C, Aimond G, Karnoub AE, et al: Lysyl oxidase is a strong determinant of tumor cell colonization in bone. Cancer Res. 77:268–278. 2017. View Article : Google Scholar

14 

Teramachi J, Nagata Y, Mohammad K, Inagaki Y, Ohata Y, Guise T, Michou L, Brown JP, Windle JJ, Kurihara N, et al: Measles virus nucleocapsid protein increases osteoblast differentiation in Paget's disease. J Clin Invest. 126:1012–1022. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Shah KM, Stern MM, Stern AR, Pathak JL, Bravenboer N and Bakker AD: Osteocyte isolation and culture methods. Bonekey Rep. 5:8382016. View Article : Google Scholar : PubMed/NCBI

16 

Park SJ, Kim MJ, Kim YK, Kim SM, Park JY and Myoung H: Combined cetuximab and genistein treatment shows additive anti-cancer effect on oral squamous cell carcinoma. Cancer Lett. 292:54–63. 2010. View Article : Google Scholar

17 

Chisholm CL, Wang H, Wong AH, Vazquez-Ortiz G, Chen W, Xu X and Deng CX: Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin. Oncotarget. 7:84439–84452. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Krebs CJ and Krawetz SA: Lysyl oxidase copper-talon complex: A model. Biochim Biophys Acta. 1202:7–12. 1993. View Article : Google Scholar : PubMed/NCBI

19 

Shih YH, Chang KW, Chen MY, Yu CC, Lin DJ, Hsia SM, Huang HL and Shieh TM: Lysyl oxidase and enhancement of cell proliferation and angiogenesis in oral squamous cell carcinoma. Head Neck. 35:250–256. 2013. View Article : Google Scholar

20 

Cox TR, Gartland A and Erler JT: Lysyl oxidase, a targetable secreted molecule involved in cancer metastasis. Cancer Res. 76:188–192. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Gartland A, Erler JT and Cox TR: The role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis. J Bone Oncol. 5:100–103. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Kim KK, Han A, Yano N, Ribeiro JR, Lokich E, Singh RK and Moore RG: Tetrathiomolybdate mediates cisplatin-induced p38 signaling and EGFR degradation and enhances response to cisplatin therapy in gynecologic cancers. Sci Rep. 5:159112015. View Article : Google Scholar : PubMed/NCBI

23 

Tang H, Leung L, Saturno G, Viros A, Smith D, Di Leva G, Morrison E, Niculescu-Duvaz D, Lopes F, Johnson L, et al: Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. Nat Commun. 8:149092017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Morisawa A, Okui T, Shimo T, Ibaragi S, Okusha Y, Ono M, Nguyen TH, Hassan NM and Sasaki A: Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. Int J Oncol 52: 989-999, 2018.
APA
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M. ... Sasaki, A. (2018). Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. International Journal of Oncology, 52, 989-999. https://doi.org/10.3892/ijo.2018.4242
MLA
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M., Nguyen, T. H., Hassan, N. M., Sasaki, A."Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma". International Journal of Oncology 52.3 (2018): 989-999.
Chicago
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M., Nguyen, T. H., Hassan, N. M., Sasaki, A."Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma". International Journal of Oncology 52, no. 3 (2018): 989-999. https://doi.org/10.3892/ijo.2018.4242
Copy and paste a formatted citation
x
Spandidos Publications style
Morisawa A, Okui T, Shimo T, Ibaragi S, Okusha Y, Ono M, Nguyen TH, Hassan NM and Sasaki A: Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. Int J Oncol 52: 989-999, 2018.
APA
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M. ... Sasaki, A. (2018). Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. International Journal of Oncology, 52, 989-999. https://doi.org/10.3892/ijo.2018.4242
MLA
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M., Nguyen, T. H., Hassan, N. M., Sasaki, A."Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma". International Journal of Oncology 52.3 (2018): 989-999.
Chicago
Morisawa, A., Okui, T., Shimo, T., Ibaragi, S., Okusha, Y., Ono, M., Nguyen, T. H., Hassan, N. M., Sasaki, A."Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma". International Journal of Oncology 52, no. 3 (2018): 989-999. https://doi.org/10.3892/ijo.2018.4242
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team