β2-microglobulin as a negative growth regulator of myeloma cells

Rui Min, Zhongkui Li, Joshua Epstein, Bart Barlogie, Qing Yi

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

High β2-microglobulin (β2m) levels in myeloma correlate with poor prognosis. We hypothesized that β2m may affect myeloma cell growth and survival. In this study, we examined the in vitro effects of β2m on myeloma cells. Primary myeloma cells freshly isolated from patients and myeloma cell lines were used, cultured in the presence of β2m, and monitored for growth and survival. β2m 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 β2m induced apoptosis and cell cycle arrest. β2m-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. β2m-induced growth arrest was associated with downregulation of cyclins A and D2. Surprisingly, anti-β2m antibodies did not block the effect of β2m but were synergistic with β2m, resulting in 90% growth inhibition and 70% apoptosis of myeloma cells. Whereas β2m treatment resulted in slight upregulation of surface β2m and major histocompatibility complex class I α-chain expression, treatment of myeloma cells with anti-β2m antibodies alone or with β2m resulted in significant downregulation of surface β2m and class I molecules, suggesting that class I molecules may be involved in signal transduction. Our data demonstrate that β2m plays an important role in regulating the growth and survival of myeloma cells in vitro and warrants further investigation to delineate the mechanisms of β2m and anti-β2m antibody-induced growth regulation of myeloma cells.

Original languageEnglish (US)
Pages (from-to)495-505
Number of pages11
JournalBritish Journal of Haematology
Volume118
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Apoptosis
  • Growth
  • Multiple myeloma
  • Tumour cells
  • β-microglobulin

ASJC Scopus subject areas

  • Hematology

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