Involvement of CD19 molecules in proliferation of human immature myeloma cells by interleukin-6
Involvement of CD19 molecules in proliferation of human immature myeloma cells by interleukin-6
批准号:
10670952
负责人:
ISHIKAWA Hideaki
金额:
$1.98万
依托单位:
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
项目状态:
已结题
起止时间:
1998 至 1999
中文摘要
Plasma cell do express CD19, whereas myeloma cell lack its expression。人类骨髓瘤细胞线KMS 5的几种稳定转染物表达CD 19基因的每种野生型或突变体,其中编码的细胞塑性区域-truncated蛋白质已被证实。与KMS 5细胞进行比较,将CD 19突变体表示为一种控制,并在SCID小鼠和锚点中增加体外、肿瘤起源性-在软琼脂上以市场方式减少CD 19表达细胞。这些结果表明,CD 19分子似乎能够调节KMS 5细胞的扩散,CD 19基因在其他骨髓瘤细胞线U266中的稳定转染者也被发现。U266细胞在白细胞介素-6(IL-6)的缺失中表达CD 19的体外增殖比控制更慢,而且与IL-6独立细胞线KMS 5中获得的结果一致。CD 19-表示U266细胞,快速反应,迅速反应到IL-6相对于控制。转录3 (STAT 3)和外链信号调节激酶1/2 (ERK 1/2)的信号转导器和激活器在U266细胞中被激活到IL-6刺激。Both activation in response to IL-6 seemed to be stronger in CD19-D1+ D1U266 than in control U266 cell。这些结果建议CD 19抑制细胞在IL-6上的增加,因为它可以增强IL-6-促进的增殖。进一步的研究如何投资CD 19 invoves the IL-6信号路径将是必要的,Non-tumorigenic U266 cells (10-D15-D1 cells)cells could be transplanted into the abdomen of SCID mice by pre-injection of agarose gels。CD 19对细胞增加的影响应该在体外进行测试,通过使用CD 19转染的U266细胞。
英文摘要
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.
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Ishikawa, H.: "Human plasma cell malignancies and Pax-5."Hematology & Oncology. 38(5). 405-410 (1999)
Ishikawa, H.:“人类浆细胞恶性肿瘤和 Pax-5。”血液学
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Ishilawa、H.: "Proliferation of immature myeloma cslls by interleukin-6 is associated with CD45 expression in himan multiple myeloma."Leukemia Lymphoma. 37. in-press (2000)
Ishilawa, H.:“白细胞介素 6 引起的未成熟骨髓瘤 csll 的增殖与人多发性骨髓瘤中的 CD45 表达相关。”《白血病淋巴瘤》37,出版中 (2000)。
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石川 秀明(分担): "別冊・医学のあゆみ 血液疾患 Ver.2 -state of arts"医歯薬出版. 3 (1998)
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Ishikawa,H.: "Induction of CD45 expression and prolideration in U-266 myeloma cell line by interleukin-6"Blood. 92・10. 3887-3897 (1998)
Ishikawa, H.:“白细胞介素 6 在 U-266 骨髓瘤细胞系中诱导 CD45 表达和增殖”血液 92·10 (1998)。
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石川 秀明(分担): "Molecular Medicine 臨時増刊号 症候・病態の分子メカニズム" 中山書店, 2 (1998)
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