在未辐照的SCID小鼠中再现与人类多发性骨髓瘤相关综合征的模型。

B. Barton, J. Cullison, J. Jackson, T. Murphy
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引用次数: 12

摘要

人类骨髓瘤细胞系被用于在体内创建人类多发性骨髓瘤模型,该模型将再现该疾病的病理生理学,包括与癌症相关的恶病质。用未辐照的严重联合免疫缺陷(SCID)小鼠作为代宿主进行体内实验,研究自分泌(人)病毒旁分泌(鼠)细胞因子对骨髓瘤发展的影响。血清中人副蛋白水平随时间和移植细胞数量的增加而增加。移植小鼠出现了与多发性骨髓瘤相关的主要综合征,恶病质和瘫痪(由于骨髓瘤细胞侵入骨骼)。从移植小鼠获得的血清样本分析显示,当小鼠终末期时,血清总蛋白平均下降20%,而血清甘油三酯平均下降50%。这些数据表明小鼠是病毒性的,尸检证实了这一点。小鼠血清中人类和小鼠白细胞介素(IL)-6、可溶性IL-6受体和小鼠IL-10的含量均较低,但可测量。这些细胞因子和血清中IL-6受体的存在也是人类骨髓瘤患者的特征。由于人类细胞对小鼠IL-6没有反应,因此有可能清楚地证明自分泌IL-6在原位形成骨髓瘤中的重要性。通过复制癌症的特征以及伴随的副肿瘤综合征,该模型应该有助于为原发性癌症以及伴随的继发性疾病设计更有效的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A model that reproduces syndromes associated with human multiple myeloma in nonirradiated SCID mice.
A human myeloma line was used to create a model of human multiple myeloma in vivo that would reproduce the pathophysiology of the disease, including the cachexia associated with cancer. Unirradiated severe combined immunodeficient (SCID) mice were used as surrogate hosts for in vivo experiments that allowed the effects of autocrine (human) verus paracrine (murine) cytokines on the development of myeloma to be studied. Serum levels of human paraprotein increased over time and with the number of cells transplanted. Transplanted mice developed major syndromes, cachexia and paralysis (due to invasion of bones by myeloma cells), associated with multiple myeloma. Analyses of serum samples obtained from transplanted mice revealed that when the mice were terminal, total serum protein decreased on average by 20%, whereas serum triglycerides decreased on average by 50%. These data indicate the mice were cachectic, which was confirmed by necropsy. The mice had low but measurable levels of both human and murine interleukin (IL)-6, soluble IL-6 receptor, and murine IL-10 in their sera. The presence of these cytokines and the IL-6 receptor in sera are also characteristics of human myeloma in patients. Since human cells do not respond to murine IL-6, it was possible to demonstrate clearly the importance of autocrine IL-6 in establishing myeloma in situ. By reproducing both the hallmarks of a cancer as well as the accompanying paraneoplastic syndromes, this model should be useful in designing more effective therapies for both the primary cancer as well as the accompanying secondary diseases.
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