The Interleukin-11 Receptor a as a Candidate Ligand-Directed Target in Osteosarcoma: Consistent Data from Cell Lines, Orthotopic Models, and Human Tumor Samples
The Interleukin-11 Receptor a as a Candidate Ligand-Directed Target in Osteosarcoma: Consistent Data from Cell Lines, Orthotopic Models, and Human Tumor Samples
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DOI：
10.1158/0008-5472.can-08-4845
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发表时间：
2009-03-01
期刊：
影响因子：
11.2
通讯作者：
Pasqualini, Renata
中科院分区：
文献类型：
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作者：
Lewis, Valerae O.;Ozawa, Michael G.;Pasqualini, Renata
白介素 11 受体 a (IL-11R α) 是骨转移的功能靶点。然而，其在原发性骨肿瘤中的作用尚未确定。因此，在这里，我们评估了 IL-11R α 作为原发性和转移性人骨肉瘤的候选靶点。首先，在原位小鼠模型中，我们发现 IL-11R α 蛋白在原发性骨和肺转移性骨肉瘤中显着表达，但在对照正常胫骨和肺中不表达。此外，全身施用展示环状九肽 CGRRAGGSC 的 IL-11R α 靶向噬菌体导致骨肉瘤中 IL-11R α 归巢噬菌体颗粒的强烈和选择性积累，但在几个对照器官中却没有。最后，大量人类原发性和转移性骨肉瘤样本中的 IL-11R α 表达与原位小鼠模型中的观察结果非常一致。这些数据确立了 IL-11R α 作为人类骨肉瘤的候选靶点，并为开发用于治疗这种恶性肿瘤的新型成像和治疗药物提供了线索。 [癌症研究 2009;69(5):1995-9]
The interleukin-11 receptor a (IL-11R alpha) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11R alpha as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that IL-11R alpha protein is markedly expressed in primary osseus and pulmonary metastatic osteosarcoma but absent from control normal tibia and lung. Moreover, systemic administration of an IL-11R alpha-targeting phage displaying the cyclic nonapeptide CGRRAGGSC resulted in strong and selective accumulation of IL-11R alpha-homing phage particles in the osteosarcoma but not in several control organs. Finally, IL-11R alpha expression in a large panel of human primary and metastatic osteosarcoma samples was remarkably consistent with the observations in the orthotopic mouse model. These data establish IL-11R alpha as a candidate target in human osteosarcoma and provide leads for the development of novel imaging and therapeutic agents for the management of this malignant tumor. [Cancer Res 2009;69(5):1995-9]