Liu Shangqin, Otsuyama Ken-ichiro, Ma Zi, Abroun Saeid, Shamsasenjan Karim, Amin Jakia, Asaoku Hideki, Kawano Michio M
Laboratory of Cellular Signal Analysis, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Int J Hematol. 2007 Jan;85(1):49-58. doi: 10.1532/IJH97.06132.
Human primary myeloma cells are well known to be heterogeneous with regard to morphology and surface phenotype. We confirmed the heterogeneous expression of such multilineage markers as CD33, CD7, CD56, CD4, and CD86 in primary myeloma cells from 20 patients with multiple myeloma and in 8 human myeloma cell lines. CD33 expression in the Liu01 cell line, a subclone of U266 cells, and in vitamin D3-treated ILKM3 cells, correlated with a monocytoid morphology featuring convoluted nuclei and with increased C/EBPalpha expression. CD56+ myeloma cells from some myeloma patients and the CD56+ (but not the CD56-) myeloma cell lines expressed neuronal cell markers, such as neuron-specific enolase and beta-tubulin III. CD7 expression in Liu01 cells and forskolin-stimulated U266 cells coincided with the presence of large cytoplasmic granules, and these cells featured increased expression of perforin messenger RNA and significant natural killer cell activity. Interleukin 6 (IL-6), a growth factor for myeloma cells, down-regulated CD33, CD7, or CD56 expression in primary myeloma cells, as well as in Liu01 cells. Therefore, these data suggest that human myeloma cells are capable of inducing the expression of multilineage markers and that IL-6 can down-regulate such expression.
众所周知,人类原发性骨髓瘤细胞在形态和表面表型方面具有异质性。我们证实了20例多发性骨髓瘤患者的原发性骨髓瘤细胞以及8种人类骨髓瘤细胞系中CD33、CD7、CD56、CD4和CD86等多谱系标志物的异质性表达。U266细胞的亚克隆Liu01细胞系以及经维生素D3处理的ILKM3细胞中的CD33表达,与具有卷曲核的单核细胞样形态以及C/EBPα表达增加相关。一些骨髓瘤患者的CD56+骨髓瘤细胞以及CD56+(而非CD56-)骨髓瘤细胞系表达神经元细胞标志物,如神经元特异性烯醇化酶和β-微管蛋白III。Liu01细胞和福斯可林刺激的U266细胞中的CD7表达与大量细胞质颗粒的存在一致,并且这些细胞的穿孔素信使核糖核酸表达增加且具有显著的自然杀伤细胞活性。白细胞介素6(IL-6)作为骨髓瘤细胞的生长因子,可下调原发性骨髓瘤细胞以及Liu01细胞中CD33、CD7或CD56的表达。因此,这些数据表明人类骨髓瘤细胞能够诱导多谱系标志物的表达,并且IL-6可以下调这种表达。