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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2018 Volume 39 Issue 1

Full Size Image

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
January-2018 Volume 39 Issue 1

Full Size Image

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

Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells

  • Authors:
    • Toshiyuki Nanbu
    • Naoki Umemura
    • Emika Ohkoshi
    • Kumi Nanbu
    • Hiroshi Sakagami
    • Jun Shimada
  • View Affiliations / Copyright

    Affiliations: Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University, Sakado, Saitama 350-0283, Japan, Department of Oral Biochemistry, Asahi University School of Dentistry, Gifu 501‑0296, Japan, Department of Natural and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Aomori University, Aomori 030-0943, Japan, Meikai University Research Institute of Odontology, Sakado, Saitama 350-0283, Japan
  • Pages: 367-375
    |
    Published online on: November 21, 2017
       https://doi.org/10.3892/or.2017.6105
  • 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

The aim of the present study was to search for an effective regimen among existing chemotherapies for head and neck squamous cell carcinoma (HNSCC). Among the tested drugs, we focused on combined SN-38, which is the active metabolite produced from irinotecan hydrochloride - a type I DNA topoisomerase inhibitor - after it is metabolized by carboxylesterase in the liver and gefitinib, an EGFR tyrosine kinase inhibitor treatment, based on the ability of this combination to inhibit HNSCC cell growth. Contrary to our expectation, in vivo, there was no significant difference in tumor growth suppression between gefitinib-only treatment and gefitinib plus SN-38. However, when tumor measurements were continued after treatment ceased, we found that several tumors showed renewed growth in the gefitinib-only group. The tumors that resumed growing after treatment showed increased CD44 expression compared with tumors from the combined treatment group. Next, we investigated the mechanism whereby SN-38 and gefitinib inhibited CD44 expression in vitro. These studies revealed that the combined treatment promoted lysosomal degradation of CD44. The present study revealed that combined gefitinib and SN-38 treatment inhibits CD44 expression by promoting its lysosomal degradation in HNSCC cells. However, it is still unclear whether inhibition of CD44 expression in HNSCC cells can directly suppress tumor regrowth after therapy. Thus, it may be necessary to elucidate the relationship between the effects of these chemotherapeutic agents on CD44 expression and tumor recurrence/metastasis in future studies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Sanderson RJ and Ironside JA: Squamous cell carcinomas of the head and neck. BMJ. 325:822–827. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Stewart JS, Cohen EE, Licitra L, van Herpen CM, Khorprasert C, Soulieres D, Vodvarka P, Rischin D, Garin AM, Hirsch FR, et al: Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol. 27:1864–1871. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, et al EORTC 24971/TAX 323 Study Group, : Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 357:1695–1704. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 359:1116–1127. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Zöller M: CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 11:254–267. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA and Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 138:645–659. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Major AG, Pitty LP and Farah CS: Cancer stem cell markers in head and neck squamous cell carcinoma. Stem Cells Int. 2013:3194892013. View Article : Google Scholar : PubMed/NCBI

9 

Orian-Rousseau V: CD44, a therapeutic target for metastasising tumours. Eur J Cancer. 46:1271–1277. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H and Seiki M: Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol. 153:893–904. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Kim HR, Wheeler MA, Wilson CM, Iida J, Eng D, Simpson MA, McCarthy JB and Bullard KM: Hyaluronan facilitates invasion of colon carcinoma cells in vitro via interaction with CD44. Cancer Res. 64:4569–4576. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Golshani R, Lopez L, Estrella V, Kramer M, Iida N and Lokeshwar VB: Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44. Cancer Res. 68:483–491. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Ohkoshi E and Umemura N: Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells. Int J Oncol. 50:387–395. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Joshua B, Kaplan MJ, Doweck I, Pai R, Weissman IL, Prince ME and Ailles LE: Frequency of cells expressing CD44, a head and neck cancer stem cell marker: Correlation with tumor aggressiveness. Head Neck. 34:42–49. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 17:211–215. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Chou TC: Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70:440–446. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 58:621–681. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Guo B, Cao S, Tóth K, Azrak RG and Rustum YM: Overexpression of Bax enhances antitumor activity of chemotherapeutic agents in human head and neck squamous cell carcinoma. Clin Cancer Res. 6:718–724. 2000.PubMed/NCBI

19 

Stewart CF, Leggas M, Schuetz JD, Panetta JC, Cheshire PJ, Peterson J, Daw N, Jenkins JJ III, Gilbertson R, Germain GS, et al: Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res. 64:7491–7499. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Azrak RG, Cao S, Durrani FA, Toth K, Bhattacharya A and Rustum YM: Augmented therapeutic efficacy of irinotecan is associated with enhanced drug accumulation. Cancer Lett. 311:219–229. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A and Bernards R: Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 483:100–103. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Kokko LL, Hurme S, Maula SM, Alanen K, Grénman R, Kinnunen I and Ventelä S: Significance of site-specific prognosis of cancer stem cell marker CD44 in head and neck squamous-cell carcinoma. Oral Oncol. 47:510–516. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Qin D, Gan Y, Shao K, Wang H, Li W, Wang T, He W, Xu J, Zhang Y, Kou Z, et al: Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. J Biol Chem. 283:33730–33735. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, et al: Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell. 145:183–197. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF and Ailles LE: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 104:pp. 973–978. 2007; View Article : Google Scholar : PubMed/NCBI

26 

Faber A, Barth C, Hörmann K, Kassner S, Schultz JD, Sommer U, Stern-Straeter J, Thorn C and Goessler UR: CD44 as a stem cell marker in head and neck squamous cell carcinoma. Oncol Rep. 26:321–326. 2011.PubMed/NCBI

27 

Giancotti FG: Mechanisms governing metastatic dormancy and reactivation. Cell. 155:750–764. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Cohen EE, Kane MA, List MA, Brockstein BE, Mehrotra B, Huo D, Mauer AM, Pierce C, Dekker A and Vokes EE: Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 11:8418–8424. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Haakenson JK, Khokhlatchev AV, Choi YJ, Linton SS, Zhang P, Zaki PM, Fu C, Cooper TK, Manni A, Zhu J, et al: Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells. J Biol Chem. 290:8632–8643. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Chinn SB, Darr OA, Owen JH, Bellile E, McHugh JB, Spector ME, Papagerakis SM, Chepeha DB, Bradford CR, Carey TE, et al: Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma. Head Neck. 37:317–326. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Oliveira LR, Castilho-Fernandes A, Oliveira-Costa JP, Soares FA, Zucoloto S and Ribeiro-Silva A: CD44+/CD133+ immunophenotype and matrix metalloproteinase-9: Influence on prognosis in early-stage oral squamous cell carcinoma. Head Neck. 36:1718–1726. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Nanbu T, Umemura N, Ohkoshi E, Nanbu K, Sakagami H and Shimada J: Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells. Oncol Rep 39: 367-375, 2018.
APA
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., & Shimada, J. (2018). Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells. Oncology Reports, 39, 367-375. https://doi.org/10.3892/or.2017.6105
MLA
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., Shimada, J."Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells". Oncology Reports 39.1 (2018): 367-375.
Chicago
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., Shimada, J."Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells". Oncology Reports 39, no. 1 (2018): 367-375. https://doi.org/10.3892/or.2017.6105
Copy and paste a formatted citation
x
Spandidos Publications style
Nanbu T, Umemura N, Ohkoshi E, Nanbu K, Sakagami H and Shimada J: Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells. Oncol Rep 39: 367-375, 2018.
APA
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., & Shimada, J. (2018). Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells. Oncology Reports, 39, 367-375. https://doi.org/10.3892/or.2017.6105
MLA
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., Shimada, J."Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells". Oncology Reports 39.1 (2018): 367-375.
Chicago
Nanbu, T., Umemura, N., Ohkoshi, E., Nanbu, K., Sakagami, H., Shimada, J."Combined SN-38 and gefitinib treatment promotes CD44 degradation in head and neck squamous cell carcinoma cells". Oncology Reports 39, no. 1 (2018): 367-375. https://doi.org/10.3892/or.2017.6105
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