AUTOCRINE GENERATION AND REQUIREMENT OF BSF-2/IL-6 FOR HUMAN MULTIPLE MYELOMAS
AUTOCRINE GENERATION AND REQUIREMENT OF BSF-2/IL-6 FOR HUMAN MULTIPLE MYELOMAS
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DOI：
10.1038/332083a0
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发表时间：
1988-03-03
期刊：
影响因子：
64.8
通讯作者：
KISHIMOTO, T
中科院分区：
文献类型：
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作者：
KAWANO, M;HIRANO, T;KISHIMOTO, T
人B细胞刺激因子2（BSF-2）最初被鉴定和分离为T细胞衍生因子，可使活化的B细胞终末成熟为免疫球蛋白产生细胞1，2。互补DNA的分子克隆预测BSF-2是一种相对分子质量（Mr）为26，000的蛋白质，与干扰素β2、杂交瘤浆细胞瘤生长因子和肝细胞刺激因子3 -7相似或相同。IL-6已被提议作为该分子的名称8，9。现在已知BSF-2具有多种生物学功能，并且其靶细胞不限于正常B细胞1，10。在T细胞11、12、浆细胞瘤6、肝细胞7、13、造血干细胞14、成纤维细胞15和大鼠嗜铬细胞瘤PC 12中也观察到应答（Satoh，T.et al.，手稿正在编写中）。本报告特别感兴趣的是，人BSF-2是鼠浆细胞瘤和杂交瘤的有效生长因子6，8，10。这一观察结果提示，BSF-2或其受体的组成型表达可能是人类骨髓瘤产生的原因。在这项研究中，我们报告说，骨髓瘤细胞新鲜分离的患者产生BSF-2和表达其受体。此外，抗BSF-2抗体抑制骨髓瘤细胞的体外生长。这是自分泌环在人类骨髓瘤发生中起作用的直接证据。
Human B cell stimulatory factor 2 (BSF-2) was originally charac-terized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells1,2. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferonβ2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor3–7. IL-6 has been proposed as a name for this molecule8,9. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells1,10. Responses are also seen in T cells11,12, plasmacytomas6, hepatocytes7,13, haematopoietic stem cells14, fibroblasts15and rat phoeochromocytoma, PC 12 (Satoh, T.et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas6,8,10. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits thein vitrogrowth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.