Expression and role of MHC class I-related chain in myeloma cells.
BACKGROUND
The molecular mechanism of natural killer (NK) cell cytotoxicity to myeloma cells remains unclear. We investigated whether MHC class I-related chain (MIC), a ligand of NKG2D that is an activating NK cell receptor, is involved in the cytotoxicity of NK cells toward myeloma cells, and examined the effects of various drugs on the cytotoxicity.


METHODS
Two human myeloma cell lines and fresh myeloma cells from 10 patients were used. MIC expression was examined by flow cytometry and reverse transcription (RT)-PCR. NK cell cytotoxicity was examined using a 51Cr-release assay. The effects of various drugs, including thalidomide, all-trans retinoic acid, dexamethasone, IFN-alpha and incadronate, on the MIC expression and NK cell cytotoxicity were examined.


RESULTS
MIC was highly expressed on the human myeloma cell lines U266 and RPMI-8226 and in myeloma cells of one of 10 patients examined. MIC expression on these cells was not changed by various drugs except IFN-alpha, by which MIC expression was down-regulated. Although MIC and HLA class I molecules were similarly expressed at high levels on both cell lines, U266 was sensitive to NK cells whereas RPMI-8226 was not. Furthermore, cytolysis by NK cells was not inhibited by the addition of anti-MIC Ab or decreased expression of MIC caused by IFN-alpha.


CONCLUSIONS
MIC plays a role in the cytolysis by NK cells in multiple myeloma.
Okamoto
M
M
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. okamotom@koto.kpu-m.ac.jp
Inaba
T
T
Yamada
N
N
Uchida
R
R
Fuchida
S-I
SI
Okano
A
A
Shimazaki
C
C
Taniwaki
M
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016898:Interferon-alpha / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; C099187:MHC class I-related chain A; C098080:MICB antigen