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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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December 2012 Volume 41 Issue 6

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Article

Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner

  • Authors:
    • Naoko Yamada
    • Koji Yamanegi
    • Hideki Ohyama
    • Masaki Hata
    • Keiji Nakasho
    • Hiroyuki Futani
    • Haruki Okamura
    • Nobuyuki Terada
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Orthopedic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
  • Pages: 2005-2012
    |
    Published online on: September 18, 2012
       https://doi.org/10.3892/ijo.2012.1630
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Abstract

Tumor cells express NKG2D ligands on their cell surface, which are the ligands of the activating receptor, NKG2D, that is expressed on the surface of NK cells. The binding of NK cells to tumor cells through the interaction of NKG2D and its ligands induces the cytolysis of the tumor cells. In the present study, we investigated the effects of hypoxia on the expression of NKG2D ligands on the surface of human osteosarcoma cells using three cell lines. To produce hypoxic and normoxic conditions, the osteosarcoma cell lines were cultured under 1 and 20% O2 conditions, respectively. The osteosarcoma cells expressed NKG2D ligands such as MHC class I-related chain molecules A and B (MICA and MICB) and the UL16-binding proteins 1, 2 and 3 (ULBP 1, 2 and 3). MICA was the most frequently expressed NKG2D ligand in the osteosarcoma cells. Hypoxia decreased the expression of cell surface MICA only without increasing the secretion of soluble MICA, which is produced by proteolytic cleavage of cell surface MICA. Hypoxia consistently decreased the susceptibility of the osteosarcoma cells to the cytotoxicity of the NK cells. Hypoxia induced the expression of hypoxia-inducible factor-1α (HIF-1α), and knockdown of the expression of HIF-1α using small interfering RNA increased the expression of cell surface MICA and concomitantly increased the level of soluble MICA. Hypoxia decreased the production of nitric oxide (NO) metabolites (nitrite and nitrate), thus, indicating a decreasing effect on NO production. However, a NO donor, NOC18, decreased the expression of cell surface MICA without any apparent effects on the expression of HIF-1α under both hypoxic and normoxic conditions. The present results indicate that hypoxia downregulates the expression of cell surface MICA without increasing the level of soluble MICA in a HIF-1α-dependent manner and suggest that the effects of hypoxia are not linked to the hypoxia-induced reduction of NO production.
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1. 

Chouaib S, Messai Y, Couve S, Escudier B, Hasmim M and Noman MZ: Hypoxia promotes tumor growth in linking angiogenesis to immune escape. Front Immunol. 3:1–10. 2012. View Article : Google Scholar : PubMed/NCBI

2. 

Wilson WR and Hay MP: Targeting hypoxia in cancer therapy. Nat Rev Cancer. 11:393–410. 2011. View Article : Google Scholar

3. 

Höckel M and Vaupel P: Tumor hypoxia: definitions and current clinical, biologic and molecular aspects. J Natl Cancer Inst. 93:266–276. 2001.PubMed/NCBI

4. 

Melillo G: Inhibiting hypoxia-inducible factor 1 for cancer therapy. Mol Cancer Res. 4:601–605. 2006. View Article : Google Scholar : PubMed/NCBI

5. 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar

6. 

Semenza GL: Involvement of hypoxia-inducible factor 1 in human cancer. Intern Med. 41:79–83. 2002. View Article : Google Scholar : PubMed/NCBI

7. 

Giaccia A, Siim BG and Johnson RS: HIF-1 as a target for drug development. Nat Rev Drug Discov. 2:803–811. 2003. View Article : Google Scholar : PubMed/NCBI

8. 

Waldhauer I and Steinle A: NK cells and cancer immunosurveillance. Oncogene. 27:5932–5943. 2008. View Article : Google Scholar : PubMed/NCBI

9. 

Nausch N and Cerwenka A: NKG2D ligands in tumor immunity. Oncogene. 27:5944–5958. 2008. View Article : Google Scholar : PubMed/NCBI

10. 

Salih HR, Rammensee H-G 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

11. 

Salih HR, Goehlsdorf D and Steinle A: Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Hum Immunol. 67:188–195. 2006. View Article : Google Scholar : PubMed/NCBI

12. 

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

13. 

Boutet P, Agüera-González S, Atkinson S, Pennington CJ, Edwards DR, Murphy G, Reyburn HT and Valés-Gómez M: Cutting edge: the metalloproteinase ADAM17/TNF-α-converting enzyme regulates proteolytic shedding of the MHC class I-related chain B protein. J Immunol. 182:49–53. 2009.PubMed/NCBI

14. 

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

15. 

Raffaghello L, Prigione I, Airoldi I, Camoriano M, Levreri I, Gambini C, Pende D, Steinle A, Ferrone S and Pistoia V: 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

16. 

Märten A, von Lilienfeld-Toal M, Büchler MW and Schmidt J: Soluble MIC is elevated in the serum of patients with pancreatic carcinoma diminishing γδT cell cytotoxicity. Int J Cancer. 119:2359–2365. 2006.PubMed/NCBI

17. 

Lee CT, Mace T and Repasky EA: Hypoxia-driven immunosuppression: a new reason to use thermal therapy in the treatment of cancer? Int J Hyperthermia. 26:232–246. 2010. View Article : Google Scholar : PubMed/NCBI

18. 

Siemens DR, Hu N, Sheikhi AK, Chung E, Frederiksen LJ, Pross H and Graham CH: Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: role of nitric oxide. Cancer Res. 68:4746–4753. 2008. View Article : Google Scholar : PubMed/NCBI

19. 

Barsoum IB, Hamilton TK, Li X, Cotechini T, Miles EA, Siemens DR and Graham CH: Hypoxia induces escape from innate immunity in cancer cells via increased expression of ADAM10: role of nitric oxide. Cancer Res. 71:7433–7441. 2011. View Article : Google Scholar : PubMed/NCBI

20. 

Postovit LM, Adams MA, Lash GE, Heaton JP and Graham CH: Oxygen-mediated regulation of tumor cell invasiveness. Involvement of a nitric oxide signaling pathway. J Biol Chem. 277:35730–35737. 2002. View Article : Google Scholar : PubMed/NCBI

21. 

Postovit LM, Sullivan R, Adams MA and Graham CH: Nitric oxide signalling and cellular adaptations to changes in oxygenation. Toxicology. 208:235–248. 2005. View Article : Google Scholar : PubMed/NCBI

22. 

Postovit LM, Adams MA, Lash GE, Heaton JP and Graham CH: Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis. Int J Cancer. 108:47–53. 2004. View Article : Google Scholar : PubMed/NCBI

23. 

Yoon SY, Lee YJ, Seo JH, Sung HJ, Park KH, Choi IK, Kim SJ, Oh SC, Choi CW, Kim BS, Shin SW, Kim YH and Kim JS: uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA-MB-231 breast carcinoma cell line. Cell Res. 16:75–81. 2006. View Article : Google Scholar : PubMed/NCBI

24. 

Quintero M, Brennan PA, Thomas GJ and Moncada S: Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation. Cancer Res. 66:770–774. 2006. View Article : Google Scholar : PubMed/NCBI

25. 

Luo L, Lu J, Wei L, Long D, Guo JY, Shan J, Li FS, Lu PY, Li PY and Feng L: The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation. BMC Cell Biol. 11:1–13. 2010.PubMed/NCBI

26. 

Wei L, Lu J, Feng L, Long D, Shan J, Li S and Li Y: HIF-1alpha accumulation upregulates MICA and MICB expression on human cardiomyocytes and enhances NK cell cytotoxicity during hypoxia-reoxygenation. Life Sci. 87:111–119. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yamada N, Yamanegi K, Ohyama H, Hata M, Nakasho K, Futani H, Okamura H and Terada N: Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner. Int J Oncol 41: 2005-2012, 2012.
APA
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H. ... Terada, N. (2012). Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner. International Journal of Oncology, 41, 2005-2012. https://doi.org/10.3892/ijo.2012.1630
MLA
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H., Okamura, H., Terada, N."Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner". International Journal of Oncology 41.6 (2012): 2005-2012.
Chicago
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H., Okamura, H., Terada, N."Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner". International Journal of Oncology 41, no. 6 (2012): 2005-2012. https://doi.org/10.3892/ijo.2012.1630
Copy and paste a formatted citation
x
Spandidos Publications style
Yamada N, Yamanegi K, Ohyama H, Hata M, Nakasho K, Futani H, Okamura H and Terada N: Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner. Int J Oncol 41: 2005-2012, 2012.
APA
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H. ... Terada, N. (2012). Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner. International Journal of Oncology, 41, 2005-2012. https://doi.org/10.3892/ijo.2012.1630
MLA
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H., Okamura, H., Terada, N."Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner". International Journal of Oncology 41.6 (2012): 2005-2012.
Chicago
Yamada, N., Yamanegi, K., Ohyama, H., Hata, M., Nakasho, K., Futani, H., Okamura, H., Terada, N."Hypoxia downregulates the expression of cell surface MICA without increasing soluble MICA in osteosarcoma cells in a HIF-1α-dependent manner". International Journal of Oncology 41, no. 6 (2012): 2005-2012. https://doi.org/10.3892/ijo.2012.1630
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