Involvement of CD19 molecules in proliferation of human immature myeloma cells by interleukin-6

CD19分子参与白细胞介素6对人未成熟骨髓瘤细胞增殖的影响

基本信息

批准号：
10670952
负责人：
ISHIKAWA Hideaki
金额：
$ 1.98万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670952/
关键词：
myeloma CD19 IL-6 STAT3 ERK1 2 cell proliferation signal transduction SCID mice CD45 MAPK

项目摘要

Plasma cells do express CD19, whereas myeloma cells lack its expression. Several stable transfectants of human myeloma cell line KMS5 expressing either wild type or mutant of the CD19 genes which encodes the cytoplasmic region-truncated protein were established. Compared with KMS5 cells expressing the CD19 mutants as a control, the proliferation in vitro, tumorigenicity in SCID mice and anchorage-independent growth in soft agar were markedly reduced in CD19-expressing cells. These results indicate that the CD19 molecule seems to regulate neagtively the proliferation of KMS5 cells.Stable transfectants of the CD19 genes into other myeloma cell line U266 were also obtained. The in vitro proliferation in the absence of interleukin-6 (IL-6) of U266 cells expressing CD19 was slower than that of control, consistent with the result obtained from the IL-6-independent cell line KMS5. The CD19-expressing U266 cells, however, proliferated rapidly in response to IL-6 relative to control. Signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated following to IL-6 stimulation in U266 cells. Both activation in response to IL-6 seemed to be stronger in CD19ィイD1+ィエD1U266 than in control U266 cells. These results suggest that CD19 inhibits cell proliferation independent on IL-6, whereas it enhances the IL-6-promoted proliferation of myeloma cells. Further studies investigating how CD19 invoves the IL-6 signaling pathways will be necessary.Non-tumorigenic U266 cells (10ィイD15ィエD1 cells) could be transplanted into the abdomen of SCID mice by pre-injection of agarose gels. The effect of CD19 on cell proliferation observed in vitro should be examined in vivo by using the CD19-transfected U266 cells.

浆细胞确实表达CD19，而骨髓瘤细胞缺乏其表达，与表达CD19的KMS5细胞相比，建立了表达编码胞质区域截短蛋白的CD19基因的野生型或突变体的几种稳定转染子。作为对照的突变体，表达CD19的细胞的体外增殖、SCID小鼠的致瘤性和软琼脂中的贴壁非依赖性生长均显着降低。结果表明CD19分子似乎负调节KMS5细胞的增殖。还获得了CD19基因稳定转染到其他骨髓瘤细胞系U266中的U266在不存在白细胞介素6(IL-6)的情况下的体外增殖。表达CD19的细胞比对照慢，与从不依赖IL-6的细胞系KMS5获得的结果一致。然而，相对于对照，U266 细胞中的信号转导器和转录激活剂 3 (STAT3) 和细胞外信号调节激酶 1/2 (ERK1/2) 在受到 IL-6 刺激后迅速增殖。 CD19D1+D1U266 细胞中对 IL-6 的反应似乎比对照 U266 细胞更强。这些结果表明 CD19 抑制细胞增殖不依赖于细胞增殖。 IL-6，而它可以增强 IL-6 促进的骨髓瘤细胞增殖，因此有必要进一步研究 CD19 如何参与 IL-6 信号通路。非致瘤性 U266 细胞（10D15D1 细胞）可以移植到骨髓瘤细胞的腹部。通过预注射琼脂糖凝胶对 SCID 小鼠体外观察到的 CD19 对细胞增殖的影响应使用体内检查。 CD19转染的U266细胞。