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
July-2014 Volume 32 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
July-2014 Volume 32 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

Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D

  • Authors:
    • Hyunkeun Song
    • Hyunjin Park
    • Gabin Park
    • Yeong Seok Kim
    • Hyun-Kyung Lee
    • Dong-Hoon Jin
    • Hyung-Sik Kang
    • Dae-Ho Cho
    • Daeyoung Hur
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea, Institute for Innovative Cancer Research, College of Medicine, University of Ulsan, Asan Medical Center, Seoul 138-736, Republic of Korea, School of Biological Sciences and Technology, Chonnam National University, Buk-gu, Gwangju 500-757, Republic of Korea, Department of Life Science, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea
  • Pages: 425-430
    |
    Published online on: May 16, 2014
       https://doi.org/10.3892/or.2014.3191
  • 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

Corticotropin-releasing factor (CRF), a coordinator of the body's responses to stress, is found in various cancer tissues and cell lines. However, the exact abilities of CRF to manipulate natural killer (NK) cells during immune response have not been studied. NKG2D is an activating receptor that is expressed on most NK and CD8+ T cells. MHC class I-related chain A (MICA) and UL16-binding protein (ULBP) 1, 2 and 3 are well-known ligands for NKG2D. In the present study, we reported our findings regarding the role of CRF in cervical cancer cell survival. Human cervical cancer cell line, HeLa cells, had significantly higher intracellular expression of UL16-binding protein 2 (ULBP2) following CRF treatment but had only slightly increased surface expression of ULBP2. Notably, MMPi (pan-metalloproteases inhibitor) blocked the release of ULBP2 molecules from the surface of HeLa cells. Furthermore, incubating NK cells with culture supernatants from CRF-treated HeLa cells, which contained soluble NKG2D ligand, reduced NK cell activity by decreasing surface expression of NKG2D. Collectively, downregulation of NKG2D by CRF-induced soluble NKG2D ligand provides a potential mechanism by which cervical cancer cells escape NKG2D-mediated attack under stress conditions.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ciocca DR, Puy LA, Fasoli LC, et al: Corticotropin-releasing hormone, luteinizing hormone-releasing hormone, growth hormone-releasing hormone, and somatostatin-like immunoreactivities in biopsies from breast cancer patients. Breast Cancer Res Treat. 15:175–184. 1990. View Article : Google Scholar

2 

Reubi JC, Waser B, Vale W and Rivier J: Expression of CRF1 and CRF2 receptors in human cancers. J Clin Endocrinol Metab. 88:3312–3320. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Sato H, Nagashima Y, Chrousos GP, Ichihashi M and Funasak Y: The expression of corticotropin-releasing hormone in melanoma. Pigment Cell Res. 15:98–103. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Arcuri F, Cintorino M, Florio P, et al: Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma. Prostate. 52:167–172. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Florio P, De Falco G, Leucci E, et al: Urocortin expression is downregulated in human endometrial carcinoma. J Endocrinol. 190:99–105. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Iino K, Sasano H, Oki Y, et al: Urocortin expression in human pituitary gland and pituitary adenoma. J Clin Endocrinol Metab. 82:3842–3850. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Graziani G, Tentori L, Muzi A, et al: Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype. Mol Cell Endocrinol. 264:44–49. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Carlson KW, Nawy SS, Wei ET, et al: Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs. Anticancer Res. 21:1173–1179. 2001.PubMed/NCBI

9 

Arbiser JL, Karalis K, Viswanathan A, et al: Corticotropin-releasing hormone stimulates angiogenesis and epithelial tumor growth in the skin. J Invest Dermatol. 113:838–842. 1999. View Article : Google Scholar : PubMed/NCBI

10 

Yang Y, Park H, Kim TS, Bang SI and Cho D: Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2 pathway in murine melanoma cell line, B16F10. Exp Dermatol. 16:22–27. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Radulovic M, Hippel C and Spiess J: Corticotropin-releasing factor (CRF) rapidly suppresses apoptosis by acting upstream of the activation of caspases. J Neurochem. 84:1074–1085. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Trinchieri G: Biology of natural killer cells. Adv Immunol. 47:187–376. 1989. View Article : Google Scholar : PubMed/NCBI

13 

Raulet DH: Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol. 5:996–1002. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Bahram S, Inoko H, Shiina T and Radosavljevic M: MIC and other NKG2D ligands: from none to too many. Curr Opin Immunol. 17:505–509. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Groh V, Steinle A, Bauer S and Spies T: Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science. 279:1737–1740. 1998.

16 

Raulet DH: Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol. 3:781–790. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Welte SA, Sinzger C, Lutz SZ, et al: Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein. Eur J Immunol. 33:194–203. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Groh V, Wu J, Yee C and Spies T: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 419:734–738. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Pende D, Rivera P, Marcenaro S, et al: Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res. 62:6178–6186. 2002.

20 

Waldhauer I, Goehlsdorf D, Gieseke F, et al: Tumor-associated MICA is shed by ADAM proteases. Cancer Res. 68:6368–6376. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Salih HR, Antropius H, Gieseke F, et al: Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood. 102:1389–1396. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Salih HR, Holdenrieder S and Steinle A: Soluble NKG2D ligands: prevalence, release, and functional impact. Front Biosci. 13:3448–3456. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Song H, Kim J, Cosman D and Choi I: Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D expression. Cell Immunol. 239:22–30. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Lichtenfels R, Biddison WE, Schulz H, Vogt AB and Martin R: CARE-LASS (calcein-release-assay), an improved fluorescence-based test system to measure cytotoxic T lymphocyte activity. J Immunol Methods. 172:227–239. 1994. View Article : Google Scholar : PubMed/NCBI

25 

Waldhauer I and Steinle A: Proteolytic release of soluble UL16-binding protein 2 from tumor cells. Cancer Res. 66:2520–2526. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Bale TL and Vale WW: CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol. 44:525–557. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Klimaviciute A, Calciolari J, Bertucci E, et al: Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state. Reprod Biol Endocrinol. 4:292006. View Article : Google Scholar : PubMed/NCBI

28 

Minas V, Rolaki A, Kalantaridou SN, et al: Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation. Br J Cancer. 97:637–645. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Cerwenka A and Lanier LL: Ligands for natural killer cell receptors: redundancy or specificity. Immunol Rev. 181:158–169. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Diefenbach A and Raulet DH: Strategies for target cell recognition by natural killer cells. Immunol Rev. 181:170–184. 2001. View Article : Google Scholar : PubMed/NCBI

31 

Lanier LL: NKG2D. J Biol Regul Homeost Agents. 17:338–340. 2003.

32 

López-Soto A, Quiñones-Lombraña A, López-Arbesú R, López-Larrea C and González S: Transcriptional regulation of ULBP1, a human ligand of the NKG2D receptor. J Biol Chem. 281:30419–30430. 2006.PubMed/NCBI

33 

Rohner A, Langenkamp U, Siegler U, Kalberer CP and Wodnar-Filipowicz A: Differentiation-promoting drugs up-regulate NKG2D ligand expression and enhance the susceptibility of acute myeloid leukemia cells to natural killer cell-mediated lysis. Leuk Res. 31:1393–1402. 2007. View Article : Google Scholar

34 

Raffaghello L, Prigione I, Airoldi I, et al: Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia. 6:558–568. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Salih HR, Rammensee HG and Steinle A: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol. 169:4098–4102. 2002. View Article : Google Scholar : PubMed/NCBI

36 

Wu JD, Higgins LM, Steinle A, Cosman D, Haugk K and Plymate SR: Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J Clin Invest. 114:560–568. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Onda H, Ohkubo S, Shintani Y, et al: A novel secreted tumor antigen with a glycosylphosphatidylinositol-anchored structure ubiquitously expressed in human cancers. Biochem Biophys Res Commun. 285:235–243. 2001. View Article : Google Scholar : PubMed/NCBI

38 

Fernández-Messina L, Ashiru O, Boutet P, et al: Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands. J Biol Chem. 285:8543–8551. 2010.PubMed/NCBI

39 

Dubicke A, Akerud A, Sennstrom M, et al: Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts. Mol Hum Reprod. 14:641–647. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Li W and Challis JR: Corticotropin-releasing hormone and urocortin induce secretion of matrix metalloproteinase-9 (MMP-9) without change in tissue inhibitors of MMP-1 by cultured cells from human placenta and fetal membranes. J Clin Endocrinol Metab. 90:6569–6574. 2005. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Song H, Park H, Park G, Kim YS, Lee H, Jin D, Kang H, Cho D and Hur D: Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D. Oncol Rep 32: 425-430, 2014.
APA
Song, H., Park, H., Park, G., Kim, Y.S., Lee, H., Jin, D. ... Hur, D. (2014). Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D. Oncology Reports, 32, 425-430. https://doi.org/10.3892/or.2014.3191
MLA
Song, H., Park, H., Park, G., Kim, Y. S., Lee, H., Jin, D., Kang, H., Cho, D., Hur, D."Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D". Oncology Reports 32.1 (2014): 425-430.
Chicago
Song, H., Park, H., Park, G., Kim, Y. S., Lee, H., Jin, D., Kang, H., Cho, D., Hur, D."Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D". Oncology Reports 32, no. 1 (2014): 425-430. https://doi.org/10.3892/or.2014.3191
Copy and paste a formatted citation
x
Spandidos Publications style
Song H, Park H, Park G, Kim YS, Lee H, Jin D, Kang H, Cho D and Hur D: Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D. Oncol Rep 32: 425-430, 2014.
APA
Song, H., Park, H., Park, G., Kim, Y.S., Lee, H., Jin, D. ... Hur, D. (2014). Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D. Oncology Reports, 32, 425-430. https://doi.org/10.3892/or.2014.3191
MLA
Song, H., Park, H., Park, G., Kim, Y. S., Lee, H., Jin, D., Kang, H., Cho, D., Hur, D."Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D". Oncology Reports 32.1 (2014): 425-430.
Chicago
Song, H., Park, H., Park, G., Kim, Y. S., Lee, H., Jin, D., Kang, H., Cho, D., Hur, D."Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D". Oncology Reports 32, no. 1 (2014): 425-430. https://doi.org/10.3892/or.2014.3191
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