Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

Yamanegi,Koji; Yamane,Junko; Kobayashi,Kenta; Ohyama,Hideki; Nakasho,Keiji; Yamada,Naoko; Hata,Masaki; Fukunaga,Satoru; Futani,Hiroyuki; Okamura,Haruki; Terada,Nobuyuki

doi:10.3892/or.2012.1981

Downregulation of matrix metalloproteinase-9 mRNA by valproic acid plays a role in inhibiting the shedding of MHC class I-related molecules A and B on the surface of human osteosarcoma cells

Authors:
- Koji Yamanegi
- Junko Yamane
- Kenta Kobayashi
- Hideki Ohyama
- Keiji Nakasho
- Naoko Yamada
- Masaki Hata
- Satoru Fukunaga
- Hiroyuki Futani
- Haruki Okamura
- Nobuyuki Terada
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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
Published online on: August 22, 2012 https://doi.org/10.3892/or.2012.1981
Pages: 1585-1590

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Abstract

Valproic acid, a histone deacetylase inhibitor, increases the expression of cell surface MHC class I-related chain molecules (MICs) A and B (MICA and B) in osteosarcoma cells and decreases their secretion of soluble MICA and MICB, which are produced by the proteolytic cleavage of cell surface MICs. Osteosarcoma cells have been reported to produce high levels of matrix metalloproteinase (MMP)-2 and -9. In this study, we investigated the involvement of MMP-2 and -9 in the inhibitory action of valproic acid (VPA) on the proteolytic cleavage of cell surface MICs using the U-2 OS and SaOS-2 osteosarcoma cell lines. VPA caused a marked decrease in the expression of MMP-9 mRNA in the U-2 OS and SaOS-2 cells and in the expression of MMP-2 mRNA in the U-2 OS cells, but only a slight decrease in the expression of MMP-2 mRNA in the SaOS-2 cells. The transfection of small interfering RNA (siRNA) for MMP-9 decreased the secretion of soluble MICA and MICB by both U-2 OS and SaOS-2 cells, but that of siRNA for MMP-2 did not. The present study therefore demonstrates that the downregulation of MMP-9 mRNA by VPA plays a role in the inhibitory action of VPA on the secretion of soluble MICA and MICB in osteosarcoma cells.

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