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.

Abstract:

: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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Yamanegi K,Yamane J,Kobayashi K,Kato-Kogoe N,Ohyama H,Nakasho K,Yamada N,Hata M,Nishioka T,Fukunaga S,Futani H,Okamura H,Terada N

doi

10.3892/or_00001026

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1621-7

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

24

pub_type

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