Exp Mol Med.  2006 Oct;38(5):474-484.

Increase of NKG2D ligands and sensitivity to NK cell-mediated cytotoxicity of tumor cells by heat shock and ionizing radiation

Affiliations
  • 1Department of Biochemistry, Pusan National University School of Medicine, Pusan, Korea. ksh7738@pusan.ac.kr
  • 2Department of Internal Medicine, Pusan National University School of Medicine, Pusan, Korea.
  • 3Department of Laboratory?Medicine, Pusan National University School of Medicine, Pusan, Korea.
  • 4Medical Research Center for Ischemic Tissue Regeneration, Pusan National University School of Medicine, Pusan, Korea.
  • 5Busan Regional Cancer Center, Pusan National University Hospital, Pusan, Korea.
  • 6Medical Research Institute, Pusan National University, Busan, Korea.
  • 7Research and Development Center, BINEX Co., LTD., Busan, Korea.

Abstract

In this study, we have investigated if current cancer therapeutic modalities including hyperthermia and ionizing radiation can increase the expression of NKG2D ligands in human cancer cell lines. The expressions of NKG2D ligands were induced by both heat shock and ionizing radiation in various cell lines including KM12, NCI-H23, HeLa and A375 cells with peaks at 2 h and 9 h after treatment, respectively, although inducibility of each NKG2D ligand was various depending on cell lines. During the induction of NKG2D ligands, heat shock protein 70 was induced by heat shock but not by ionizing radiation. These results were followed by increased susceptibilities to NK cell-mediated cytolysis after treatment with heat shock and ionizing radiation. These results suggest that heat shock and ionizing radiation induce NKG2D ligands and consequently might lead to increased NK cell-mediated cytotoxicity in various cancer cells.

Keyword

heat-shock response; immunotherapy, active; killer cells, natural; natural killer cell activating receptors; neoplasms; radiation, ionizing

MeSH Terms

Tumor Cells, Cultured
Receptors, Immunologic/*metabolism
Radiation, Ionizing
Neoplasms/immunology/*radiotherapy/therapy
*Ligands
Killer Cells, Natural/*immunology
Hyperthermia, Induced/methods
Humans
Hela Cells
*Heat-Shock Response/physiology
Heat
HSP70 Heat-Shock Proteins/metabolism/radiation effects
Gene Expression Regulation, Neoplastic/radiation effects
Cytotoxicity, Immunologic/*physiology/*radiation effects
Antigens, Surface/metabolism/radiation effects
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