Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4.
Tracking human multiple myeloma xenografts in NOD-Rag-1/IL-2 receptor gamma chain-null mice with the novel biomarker AKAP-4.
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DOI：
10.1186/1471-2407-11-394
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发表时间：
2011-09-16
期刊：
影响因子：
3.8
通讯作者：
Chiriva-Internati M
中科院分区：
文献类型：
--
作者：
Mirandola L;Yu Y;Jenkins MR;Chiaramonte R;Cobos E;John CM;Chiriva-Internati M
多发性骨髓瘤（MM）是血液学肿瘤中发病率排名第二的致命恶性肿瘤。正在不断努力开发创新和更有效的治疗方法。新疗法的临床前评估依赖于该疾病的小鼠模型的使用。在这里，我们描述了一种新的MM动物模型，该模型在NOD-Rag1null IL2rgnull （NRG）小鼠中支持细胞系和原代MM细胞的移植，这些细胞可以用肿瘤抗原AKAP-4跟踪。人MM细胞系U266、H929和原代MM细胞经静脉给药后成功植入NRG小鼠体内，并在肿瘤动物的骨髓、血液和脾脏中发现。AKAP-4的表达模式与已知的MM标记物（如副蛋白、CD38和CD45）相似。我们首次开发了一种小鼠模型，允许MM细胞系和原代细胞在多灶部位生长，从而模拟患者所见的疾病。此外，我们验证了使用AKAP-4抗原在体内跟踪肿瘤生长并特异性识别小鼠组织中的MM细胞。我们期望我们的模型将显著改善新的抗骨髓瘤疗法的临床前评估。
Multiple myeloma (MM) is a fatal malignancy ranking second in prevalence among hematological tumors. Continuous efforts are being made to develop innovative and more effective treatments. The preclinical evaluation of new therapies relies on the use of murine models of the disease. Here we describe a new MM animal model in NOD-Rag1null IL2rgnull (NRG) mice that supports the engraftment of cell lines and primary MM cells that can be tracked with the tumor antigen, AKAP-4. Human MM cell lines, U266 and H929, and primary MM cells were successfully engrafted in NRG mice after intravenous administration, and were found in the bone marrow, blood and spleen of tumor-challenged animals. The AKAP-4 expression pattern was similar to that of known MM markers, such as paraproteins, CD38 and CD45. We developed for the first time a murine model allowing for the growth of both MM cell lines and primary cells in multifocal sites, thus mimicking the disease seen in patients. Additionally, we validated the use of AKAP-4 antigen to track tumor growth in vivo and to specifically identify MM cells in mouse tissues. We expect that our model will significantly improve the pre-clinical evaluation of new anti-myeloma therapies.
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