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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2018 Volume 16 Issue 5

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
November-2018 Volume 16 Issue 5

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

Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells

  • Authors:
    • Bingyu Zhang
    • Jianzhong Dang
    • Diandian Ba
    • Cencen Wang
    • Juan Han
    • Fang Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 6163-6170
    |
    Published online on: August 23, 2018
       https://doi.org/10.3892/ol.2018.9354
  • 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

Extensive clinical evidence supports that cytotoxic T lymphocyte antigen‑4 (CTLA‑4) is expressed in a variety of human malignant tumour cells in addition to T cells. In certain types of cancer, the overexpression of CTLA‑4 is associated with poor patient prognosis. However, few studies have demonstrated the effects of tumour‑intrinsic CTLA‑4 in cancer stem cells, including melanoma stem cells (MSCs). In the present study, it was demonstrated that melanoma cell‑intrinsic CTLA‑4 induced tumour cell proliferation in vitro and suppressed tumour cell apoptosis. Furthermore, CTLA‑4 was expressed in aldehyde dehydrogenase (ALDH)+ MSCs. CTLA‑4 inhibited MSCs proliferation in vitro by blocking antibodies and significantly downregulated ALDH1A1, ALDH1A3 and ALDH2 mRNA expression (P<0.01). Functionally, blocking CTLA‑4 in melanoma cell lines suppressed the properties of stem‑like cells, including ALDH activity and significantly suppressed the ability of these cells to form spheres in vitro (P<0.05). In addition, the blocking of CTLA‑4 in melanoma cells suppressed the properties of stem‑like cells in vivo, including the capacity for tumourigenesis. The presence of residual ALDH+ MSCs within the tumour was observed, and the blocking CTLA‑4 significantly decreased the number of residual ALDH+ MSCs in vivo (P<0.01). Altogether, these results indicate the identification of a novel mechanism underlying melanoma progression in the present study and that CTLA‑4‑targeted therapy may benefit candidate CTLA‑4‑targeted therapy by improving the long‑term outcome for patients with advanced stages of melanoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Gray-Schopfer V, Wellbrock C and Marais R: Melanoma biology and new targeted therapy. Nature. 445:851–857. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Murphy GF, Wilson BJ, Girouard SD, Frank NY and Frank MH: Stem cells and targeted approaches to melanoma cure. Mol Aspects Med. 39:33–49. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Hirohashi Y, Torigoe T, Tsukahara T, Kanaseki T, Kochin V and Sato N: Immune responses to human cancer stem-like cells/cancer-initiating cells. Cancer Sci. 107:12–17. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Brunner MC, Chambers CA, Chan FK, Hanke J, Winoto A and Allison JP: CTLA-4-mediated inhibition of early events of T cell proliferation. J Immunol. 162:5813–5820. 1999.PubMed/NCBI

5 

Wu L, Yun Z, Tagawa T, Rey-McIntyre K and de Perrot M: CTLA-4 blockade expands infiltrating T cells and inhibits cancer cell repopulation during the intervals of chemotherapy in murine mesothelioma. Mol Cancer Ther. 11:1809–1819. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Whiteside TL: Regulatory T cell subsets in human cancer: Are they regulating for or against tumor progression? Cancer Immunol Immunother:. 63:67–72. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Lindau D, Gielen P, Kroesen M, Wesseling P and Adema GJ: The immunosuppressive tumour network: Myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 138:105–115. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 363:711–723. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, et al: Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 364:2517–2526. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Suwalska K, Pawlak E, Karabon L, Tomkiewicz A, Dobosz T, Urbaniak-Kujda D, Kuliczkowski K, Wolowiec D, Jedynak A and Frydecka I: Association studies of CTLA-4, CD28 and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population. Hum Immunol. 69:193–201. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Monne M, Piras G, Palmas A, Arru L, Murineddu M, Latte G, Noli A and Gabbas A: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism and susceptibility to non-Hodgkin's lymphoma. Am J Hematol. 76:14–18. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Yu H, Yang J, Jiao S, Li Y, Zhang W and Wang J: Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: Implications for prognosis. Cancer Immunol Immunother. 64:853–860. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Khaghanzadeh N, Erfani N, Ghayumi MA and Ghaderi A: CTLA4 gene variations and haplotypes in patients with lung cancer. Cancer Genet Cytogenet. 196:171–174. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Laurent S, Queirolo P, Boero S, Salvi S, Piccioli P, Boccardo S, Minghelli S, Morabito A, Fontana V, Pietra G, et al: The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-alpha production. J Transl Med. 11:1082013. View Article : Google Scholar : PubMed/NCBI

15 

Hadinia A, Hossieni SV, Erfani N, Saberi-Firozi M, Fattahi MJ and Ghaderi A: CTLA-4 gene promoter and exon 1 polymorphisms in Iranian patients with gastric and colorectal cancers. J Gastroenterol Hepatol. 22:2283–2287. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Pawlak E, Karabon L, Wlodarska-Polinska I, Jedynak A, Jonkisz A, Tomkiewicz A, Kornafel J, Stepien M, Ignatowicz A, Lebioda A, et al: Influence of CTLA-4/CD28/ICOS gene polymorphisms on the susceptibility to cervical squamous cell carcinoma and stage of differentiation in the Polish population. Hum Immunol. 71:195–200. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Zhang XF, Pan K, Weng DS, Chen CL, Wang QJ, Zhao JJ, Pan QZ, Liu Q, Jiang SS, Li YQ, et al: Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: Implications for prognosis. Oncotarget. 7:26670–26679. 2016.PubMed/NCBI

18 

Contardi E, Palmisano GL, Tazzari PL, Martelli AM, Falà F, Fabbi M, Kato T, Lucarelli E, Donati D, Polito L, et al: CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer. 117:538–550. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Dai F, Zhang F, Sun D, Zhang ZH, Dong SW and Xu JZ: CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation. Braz J Med Biol Res. 48:629–636. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Duarte S, Momier D, Baqué P, Casanova V, Loubat A, Samson M, Guigonis JM, Staccini P, Saint-Paul MC, De Lima MP, et al: Preventive cancer stem cell-based vaccination reduces liver metastasis development in a rat colon carcinoma syngeneic model. Stem Cells. 31:423–432. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Ning N, Pan Q, Zheng F, Teitz-Tennenbaum S, Egenti M, Yet J, Li M, Ginestier C, Wicha MS, Moyer JS, et al: Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 72:1853–1864. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Choi AR, Park JR, Kim RJ, Kim SR, Cho SD, Jung JY and Nam JS: Inhibition of Wnt1 expression reduces the enrichment of cancer stem cells in a mouse model of breast cancer. Biochem Biophys Res Commun. 425:436–442. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Li F, Guo Z, Yu H, Zhang X, Si T, Liu C, Yang X and Qi L: Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model. Neoplasma. 61:659–671. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Shinoyama M, Ideguchi M, Hayashi H, Doi D, Hashimoto N, Suzuki M and Takahashi J: Cytotoxic T lymphocyte antigen 4 immunogloblin promotes neuronal differentiation in the grafts of embryonic stem cell-derived neural precursor cells. Neuroscience. 202:484–491. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, McCarter MD, Wang J, Gonzalez R, Thompson DC, Norris DA, et al: ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets. Stem Cells. 30:2100–2113. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Topalian SL, Taube JM, Anders RA and Pardoll DM: Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 16:275–287. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Callahan MK, Postow MA and Wolchok JD: Immunomodulatory therapy for melanoma: Ipilimumab and beyond. Clin Dermatol. 31:191–199. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Ji RR, Chasalow SD, Wang L, Hamid O, Schmidt H, Cogswell J, Alaparthy S, Berman D, Jure-Kunkel M, Siemers NO, et al: An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother. 61:1019–1031. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang B, Dang J, Ba D, Wang C, Han J and Zheng F: Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells. Oncol Lett 16: 6163-6170, 2018.
APA
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., & Zheng, F. (2018). Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells. Oncology Letters, 16, 6163-6170. https://doi.org/10.3892/ol.2018.9354
MLA
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., Zheng, F."Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells". Oncology Letters 16.5 (2018): 6163-6170.
Chicago
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., Zheng, F."Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells". Oncology Letters 16, no. 5 (2018): 6163-6170. https://doi.org/10.3892/ol.2018.9354
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang B, Dang J, Ba D, Wang C, Han J and Zheng F: Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells. Oncol Lett 16: 6163-6170, 2018.
APA
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., & Zheng, F. (2018). Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells. Oncology Letters, 16, 6163-6170. https://doi.org/10.3892/ol.2018.9354
MLA
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., Zheng, F."Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells". Oncology Letters 16.5 (2018): 6163-6170.
Chicago
Zhang, B., Dang, J., Ba, D., Wang, C., Han, J., Zheng, F."Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells". Oncology Letters 16, no. 5 (2018): 6163-6170. https://doi.org/10.3892/ol.2018.9354
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