Sodium valproate, a histone deacetylase inhibitor, augments the expression of cell-surface NKG2D ligands, MICA/B, without increasing their soluble forms to enhance susceptibility of human osteosarcoma cells to NK cell-mediated cytotoxicity
| Autor: | Nobuyuki Terada, Satoru Fukunaga, Nahoko Kato-Kogoe, Hideki Ohyama, Kenta Kobayashi, Junko Yamane, Koji Yamanegi, Hiroyuki Futani, Naoko Yamada, Haruki Okamura, Keiji Nakasho, Masaki Hata, Toshihiro Nishioka |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
medicine.drug_class Bone Neoplasms Biology Ligands Natural killer cell Cell Line Tumor MHC class I medicine Humans Protein Isoforms Cytotoxicity Immunity Cellular Osteosarcoma Valproic Acid Histone deacetylase inhibitor Cell Membrane Histocompatibility Antigens Class I General Medicine NKG2D Combined Modality Therapy Up-Regulation Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors Killer Cells Natural stomatognathic diseases medicine.anatomical_structure Oncology Solubility Acetylation Cell culture NK Cell Lectin-Like Receptor Subfamily K Antigens Surface Cancer research biology.protein Histone deacetylase Immunotherapy |
| Zdroj: | Oncology reports. 24(6) |
| ISSN: | 1791-2431 |
| Popis: | MHC class I-related chain molecules A and B (MICA and B) expressed on the cell-surface of tumor cells are ligands for an activating receptor, NKG2D, expressed on natural killer (NK) cells and stimulate the NK cell-mediated cytotoxicity. On the other hand, the soluble form of MICA and B produced by proteolytic cleavage of cell-surface MIC interferes with NK cell-mediated cytotoxicity. We investigated effect of sodium valproate (VPA), a histone deacetylase inhibitor, on the production of cell-surface and soluble MICA and B and NK cell-mediated cytotoxicity in four human osteosarcoma cells. VPA at 0.5 and 1.0 mM induced acetylation of histones bound to MICA and B gene promoters, increased cell-surface but not soluble MICA and B, and augmented the susceptibility of osteosarcoma cells to NK cell-mediated cytotoxicity. The present results indicate that VPA sensitizes human osteosarcoma cells to cytotoxicity of NK cells. |
| Databáze: | OpenAIRE |
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