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Analysis of the mechanisms in multiple myeloma cell growth----Paracrine, Autocrine and Factor-independent Growth----

多发性骨髓瘤细胞生长机制分析----旁分泌、自分泌和因子非依赖性生长----

基本信息

批准号：
02670291
负责人：
SHIMIZU Shiro
金额：
$ 1.34万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

The growth mechanisms of multipje myeloma cells were studied utilizing ten estabhshed human multiple myeloma cell lines and molecular biological methods.1. Ten human multiple myeloma cell lines were established using macrophages as a feeder layer. Four of them were derived from bone marrow and the other 6 from extrarnedullary lesions.2. Bone marrow-derived ceU. 1ines grew dependently on a macrophage feeder layer or in response to interleuldn-6(IL-6). In contrast, extrameduffary lesion-derived cell lines grew independent of any feeder layers or cytokines.3. All cell lines constitutively expressed IL-6 receptor (IL-6R) mRNA and cell surface IL-6R.4. All cell lines except for AMO1 prolfferated in response to IL-6. Bone marrow-derived cell lines proliferated absolutely dependently on IL-6. Spontaneously proliferating extramedullary-lesion derived cell lines additively proliferated in response to IL-6.5. No cell lines constitutively expressed IL-6 mRNA nor secreted IL-6.6. The anti-IL-6 antibody or anti-IL-6R antibody inhibited only IL-6-induced proliferation, but did not inhibit the spontaneous proliferation of extramedullary lesion-derived cell lines.These results indicate that the IL-6 paracrine mechanism plays the central role in the growth of bone marrow-derived cell lines. In contrast, the factor-independent mechanism plays a primary role in the growth of extra meduffary lesion-derived cell lines, that also additively proliferate in response to IL-6 (paracrine mechanisms). Because no IL-6 mRNA was detected in any cell lines, the intracellular autocrine mechanism or autocrine mechanisim appeared not to be operating in any of the cell lines.

利用已建立的10株人多发性骨髓瘤细胞系和分子生物学方法，对多发性骨髓瘤细胞的生长机制进行了研究。以巨噬细胞为饲养层，建立了10株人多发性骨髓瘤细胞系。其中4例来源于骨髓，6例来源于关节外病变。骨髓源性CEU。1细胞依赖巨噬细胞饲养层生长或对白介素6(IL-6)反应。相反，外周病变来源的细胞系的生长不依赖于任何饲养层或细胞因子。所有细胞系均表达IL-6受体(IL-6R)mRNA和细胞表面IL-6R。除AMO1外，所有细胞系对IL-6的反应均增强。骨髓来源的细胞系的增殖完全依赖于IL-6。自发增殖的髓外病变来源的细胞系对IL-6.5的反应增加了增殖。没有细胞系表达IL-6mRNA，也没有分泌IL-6.6。抗IL-6抗体或抗IL-6R抗体仅抑制IL-6诱导的骨髓来源细胞的增殖，但不抑制髓外病变来源细胞系的自发增殖，提示IL-6旁分泌机制在骨髓来源细胞系的生长中起中心作用。相反，因子非依赖性机制在额外的中间病变来源的细胞系的生长中起主要作用，这些细胞系也对IL-6(旁分泌机制)做出反应而相加增殖。由于在任何细胞系中均未检测到IL-6mRNA，细胞内自分泌机制或自分泌机制似乎在任何细胞系中都不起作用。