Systemic RANK-Fc protein therapy is efficacious against primary osteosarcoma growth in a murine model via activity against osteoclasts
Systemic RANK-Fc protein therapy is efficacious against primary osteosarcoma growth in a murine model via activity against osteoclasts
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DOI：
10.1211/jpp.62.04.0009
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发表时间：
2010-04-01
影响因子：
3.3
通讯作者：
Choong, Peter F. M.
中科院分区：
文献类型：
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作者：
Akiyama, Toru;Dass, Crispin R.;Choong, Peter F. M.
目的骨肉瘤（Osteosarcoma， OS）是最常见的原发性骨恶性肿瘤，主要发生于青少年和青壮年。虽然手术和化疗对OS的治疗有了实质性的改善，但在过去的二十年中，生存率并没有进一步提高。方法研究核因子κ B配体受体激活剂（RANKL）破骨细胞（OCL）系统作为OS的生物学靶点。RANKL是OCL形成和骨吸收活性的关键因素。骨的原发病变和随后的骨肉瘤转移都需要骨细胞的诱导。RANK-Fc是一种有效的RANKL拮抗剂和OCL形成和活性抑制剂。在Balb/c nu/nu小鼠原位模型中，每周两次给药350 μ g RANK-Fc （n = 5）减少肺转移（P < 0.05），保留骨结构和降低酒石酸盐抗性酸性磷酸酶（TRAP）（+） OCLs （P < 0.05）
Objectives Osteosarcoma (OS) is the most common primary malignant bone tumour, and mainly affects adolescents and young adults. Although there has been substantial improvement in management of OS with surgery and chemotherapy, further survival increase has not been achieved over the past two decades.Methods We focused on the receptor activator of nuclear factor kappa B ligand (RANKL) osteoclast (OCL) system as a biological target for OS. RANKL is a critical factor for OCL formation and bone resorption activity. The primary lesion in bone and ensuing metastasis in OS both require the induction of OCLs. RANK-Fc is a potent RANKL antagonist and inhibitor of OCL formation and activity.Key findings In an orthotopic model in Balb/c nu/nu mice, a twice weekly dosing regimen of 350 mu g of RANK-Fc per mouse subcutaneously (n = 5) reduced lung metastasis (P>0.05), preserved bone structure and reduced tartrate-resistant acid phosphatase (TRAP)(+) OCLs (P