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

  • Published online on: September 18, 2012     https://doi.org/10.3892/ijo.2012.1630
  • Pages: 2005-2012
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

December 2012
Volume 41 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

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