权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

浆细胞表达CD19，而骨髓瘤细胞不表达。建立了几种稳定的人骨髓瘤细胞系KMS5转染物，表达编码细胞质区域截断蛋白的CD19基因的野生型或突变型。与对照表达CD19突变体的KMS5细胞相比，表达CD19突变体的细胞体外增殖、SCID小鼠的致瘤性和软琼脂中的非锚定生长均明显降低。这些结果表明CD19分子似乎负调控KMS5细胞的增殖。CD19基因稳定转染到其他骨髓瘤细胞系U266中。在缺乏白细胞介素-6 （IL-6）的情况下，表达CD19的U266细胞的体外增殖速度比对照慢，与IL-6不依赖性细胞系KMS5的结果一致。然而，与对照相比，表达cd19的U266细胞在IL-6的作用下增殖迅速。在U266细胞中，信号转导和转录激活因子3 （STAT3）和细胞外信号调节激酶1/2 （ERK1/2）在IL-6刺激后被激活。这两种激活对IL-6的反应在CD19 γ γ γ γ γ + γ γ γ γ γ + γ γ γ U266细胞中似乎比在对照U266细胞中更强。这些结果表明，CD19抑制细胞增殖不依赖于IL-6，而它增强IL-6促进骨髓瘤细胞的增殖。进一步研究CD19如何参与IL-6信号通路将是必要的。通过琼脂糖凝胶预注射，可将非致瘤性的U266细胞（10 μ l￣D15 μ l￣D1细胞）移植至SCID小鼠腹腔。体外观察到的CD19对细胞增殖的影响应该在体内用转染CD19的U266细胞来检验。