β2-microglobulin (β2m) is a single non-glycosylated protein that is non-covalently associated, on the cell surface, with the a-chain of the major histocompatibility complex (MHC) class I molecules. Free β2m is found in body fluids and elevated levels of the protein have been demonstrated in autoimmune and infectious diseases, and in malignancies including multiple myeloma (MM). MM is a B-cell neoplasia characterized by an accumulation of malignant plasma cells in the bone marrow. Myeloma cells produce β2m and the elevated levels of β2m correlate to poor prognosis of patients. The aim of the present study was to examine whether β;m at elevated levels may affect myeloma cell growth. The results show that β2m suppressed, in time- and dose-dependent manners, the growth of 3 out of 4 myeloma cell lines tested (ARK-RS, RPMI-8226 and U266). The growth inhibition was mediated via the induction of apoptosis as well as growth arrest in these myeloma cell lines. On the contrary, β2m enhanced the growth of the other cell line, ARP-1, by reducing the percentage of apoptotic cells in culture and increasing the percentage of cells in S-phase. Furthermore, β;m acts also on freshly isolated primary myeloma cells; a growth inhibition was seen in tumor cells from 3 of 7 patients, while a growth promotion in 2. Tumor cells from the remaining 2 patients did not respond to β2m treatment. β2m treatment induced a significant reduction in the density of surface β2m, while that of the α-chain of the MHC class-I molecules was not affected. Caspase inhibitors abrogated β2m-induced apoptosis in the cell lines, suggesting that the apoptosis was through the caspase cascade. Taken together, our data demonstrate that β2m plays an important role in regulating the growth and survival of myeloma cells, and warrant further investigation to delineate the mechanism of βjin-mduced growth regulation in myeloma cells.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology