Premium
β 2 ‐microglobulin as a negative growth regulator of myeloma cells
Author(s) -
Min Rui,
Li Zhongkui,
Epstein Joshua,
Barlogie Bart,
Yi Qing
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03635.x
Subject(s) - downregulation and upregulation , multiple myeloma , apoptosis , beta 2 microglobulin , antibody , cancer research , biology , cell culture , cell growth , microbiology and biotechnology , immunology , biochemistry , genetics , gene
Summary. High β 2 ‐microglobulin (β 2 m) levels in myeloma correlate with poor prognosis. We hypothesized that β 2 m may affect myeloma cell growth and survival. In this study, we examined the in vitro effects of β 2 m on myeloma cells. Primary myeloma cells freshly isolated from patients and myeloma cell lines were used, cultured in the presence of β 2 m, and monitored for growth and survival. β 2 m suppressed the growth of primary tumour cells and myeloma cell lines (ARK‐RS, ARP‐1, RPMI‐8226, U266, ARH‐77 and IM‐9). High concentrations of β 2 m induced apoptosis and cell cycle arrest. β 2 m‐induced apoptosis was dependent on activation of a caspase cascade, inhibited by interleukin 6, and did not involve the surface death receptors, as receptor‐neutralizing antibodies had no inhibitory effect. β 2 m‐induced growth arrest was associated with downregulation of cyclins A and D2. Surprisingly, anti‐β 2 m antibodies did not block the effect of β 2 m but were synergistic with β 2 m, resulting in 90% growth inhibition and 70% apoptosis of myeloma cells. Whereas β 2 m treatment resulted in slight upregulation of surface β 2 m and major histocompatibility complex class I α‐chain expression, treatment of myeloma cells with anti‐β 2 m antibodies alone or with β 2 m resulted in significant downregulation of surface β 2 m and class I molecules, suggesting that class I molecules may be involved in signal transduction. Our data demonstrate that β 2 m plays an important role in regulating the growth and survival of myeloma cells in vitro and warrants further investigation to delineate the mechanisms of β 2 m and anti‐β 2 m antibody‐induced growth regulation of myeloma cells.