Kaisho T, Oritani K, Ishikawa J, Tanabe M, Muraoka O, Ochi T, Hirano T
Division of Molecular Oncology, Osaka University Medical School, Japan.
J Immunol. 1992 Dec 15;149(12):4088-95.
In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.
为了阐明骨髓(BM)微环境在多发性骨髓瘤(MM)和类风湿关节炎(RA)中的病理意义,我们通过转染表达SV40大T抗原的质粒,建立了源自患者或健康供体(HD)的骨髓基质细胞系,并检测了它们支持前B细胞系DW34依赖基质细胞生长的能力。与源自MM和RA的骨髓基质细胞系共培养的DW34细胞回收数量的平均值,比与源自HD的细胞系共培养时多6至10倍。它们支持DW34细胞生长的能力增强并非由细胞因子(包括IL-6、IL-7和c-kit配体)引起,尽管外源性IL-7可增强生长支持能力。通过用膜滤器抑制细胞间相互作用,可消除DW34细胞在基质细胞系上的生长。流式细胞术分析显示,基质细胞系不表达LFA-1α、β、NCAM或ELAM-1。患者和HD骨髓基质细胞系均可变表达ICAM-1、VCAM-1和CD44。然而,这些分子的表面表达水平与基质细胞系支持DW34细胞生长的能力无关。综上所述,这些结果表明骨髓微环境可能在MM和RA的发病机制中起重要作用。