Takahashi T, Okuno Y, Ohsugi Y
Second Department of Internal Medicine, Faculty of Medicine, Kyoto University.
Rinsho Ketsueki. 1993 Apr;34(4):423-6.
It remains to be clarified whether IL-6 acts on the growth of human myeloma cells by an autocrine or paracrine mechanism. Even in established myeloma cell lines, the autocrine growth by IL-6 appears unusual. In the present study, we deviced a model of IL-6 autocrine growth in vitro by transfecting IL-6 cDNA into a human myeloma cell line that had a proliferative response to IL-6 but did not produce IL-6. After IL-6 transfection, the cells (S6B45) proliferated in culture media without IL-6. IL-6 production by S6B45 was demonstrated both at protein and mRNA level. The growth of S6B45 was definitely inhibited by anti-IL-6 (MH166) or anti-IL-6 receptor (PM1) monoclonal antibodies. Furthermore, S6B45 was successfully transplanted to nude mice. The transplanted tumor growth was clearly inhibited by the administration of MH166 or PM1 to the mice. The in vivo antitumor activity of these antibodies suggest a new therapeutic strategy against tumors that proliferate by an autocrine mechanism through a cytokine such as IL-6.
白细胞介素-6（IL-6）是通过自分泌还是旁分泌机制作用于人类骨髓瘤细胞的生长仍有待阐明。即使在已建立的骨髓瘤细胞系中，IL-6的自分泌生长也显得不寻常。在本研究中，我们通过将IL-6 cDNA转染到对IL-6有增殖反应但不产生IL-6的人类骨髓瘤细胞系中，构建了一种体外IL-6自分泌生长模型。转染IL-6后，细胞（S6B45）在不含IL-6的培养基中增殖。S6B45在蛋白质和mRNA水平均显示出IL-6的产生。抗IL-6（MH166）或抗IL-6受体（PM1）单克隆抗体可明确抑制S6B45的生长。此外，S6B45成功移植到裸鼠体内。给小鼠注射MH166或PM1可明显抑制移植瘤的生长。这些抗体的体内抗肿瘤活性提示了一种针对通过细胞因子如IL-6自分泌机制增殖的肿瘤的新治疗策略。
