CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models.
CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models.
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CD47 阻断可抑制异种移植模型中人骨肉瘤的肿瘤进展。
DOI：
10.18632/oncotarget.4282
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Wang YP
中科院分区：
文献类型：
--
作者：
Xu JF;Pan XH;Zhang SJ;Zhao C;Qiu BS;Gu HF;Hong JF;Cao L;Chen Y;Xia B;Bi Q;Wang YP
骨肉瘤是儿童和青少年中最常见的骨肿瘤。尽管进行了强化化疗，晚期疾病患者的预后仍然较差，这说明需要替代疗法。在这项研究中，我们探索了使用阻断 CD47 的抗体来抑制骨肉瘤的肿瘤生长。我们首先发现，与邻近的非肿瘤组织相比，8 名骨肉瘤患者的肿瘤组织中 CD47 mRNA 水平上调。进一步的蛋白质印迹（WB）和免疫组织化学（IHC）表明，与正常成骨细胞和邻近非肿瘤组织相比，CD47蛋白水平在骨肉瘤中高表达。骨肉瘤癌症干细胞标记物染色显示，大多数 CD44+ 细胞表达 CD47，尽管百分比不同（范围从 80% 到 99%）。此外，高 CD47 mRNA 表达水平与无进展生存率和总生存率降低相关。此外，特异性抗体阻断CD47可抑制骨肉瘤肿瘤细胞的侵袭能力，进一步抑制体内KRIB骨肉瘤细胞的自发性肺转移。最后，CD47 阻断增加了巨噬细胞对骨肉瘤肿瘤细胞的吞噬作用。总之，我们的研究结果证明 CD47 是骨肉瘤转移的关键调节因子，并表明通过抗 CD47 靶向抑制该抗原可能是治疗该肿瘤的一种新型免疫治疗方法。
Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells. In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.
影响因子：
3.7
作者：
Liu J;Hettmer S;Milsom MD;Hofmann I;Hua F;Miller C;Bronson RT;Wagers AJ
通讯作者：
Wagers AJ