Barut B A, Zon L I, Cochran M K, Paul S R, Chauhan D, Mohrbacher A, Fingeroth J, Anderson K C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Leuk Res. 1992 Oct;16(10):951-9. doi: 10.1016/0145-2126(92)90073-g.
The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS-Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL-6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy.
白细胞介素6（IL-6）在五种多发性骨髓瘤衍生细胞系生长中的作用得到了表征。U266和RPMI 8226细胞系在与外源性IL-6一起培养时显示出DNA合成增加，表达IL-6细胞表面受体（IL-6Rs）并表达IL-6R的mRNA。然而，这些细胞不分泌可检测到的IL-6蛋白，并且抗IL-6的中和抗体不抑制它们的生长。其他三种骨髓瘤衍生细胞系ARH-77、IM-9和HS-Sultan对外源性IL-6无反应，不分泌IL-6或不表达细胞表面IL-6Rs。对IL-6有反应的细胞系带有晚期B细胞表面抗原（Ags）、CD38和PCA-1，而那些对IL-6无反应的细胞系强烈表达B1（CD20）和B4（CD19）Ags，代表B细胞分化的早期阶段。最后，两个对IL-6有反应的细胞系不表达爱泼斯坦-巴尔病毒（EBV）蛋白；相反，在三个对IL-6无反应的细胞系中可检测到通常在潜伏期表达的EBV编码蛋白，证实了病毒感染。这些研究阐明了骨髓瘤细胞系表型和生物学中观察到的异质性，并表明表达IL-6细胞表面受体且对IL-6有反应的U266和RPMI 8226细胞系可能有助于进一步研究体内骨髓瘤中IL-6信号转导及相关的IL-6介导的生长。相比之下，那些不依赖IL-6的细胞系为进一步研究恶性肿瘤中EBV转化和IL-6依赖性生长机制提供了模型。
