IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma.

IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma.
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DOI:
10.1016/j.canlet.2013.05.002
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发表时间:
2013-08-09
期刊:
影响因子:
9.7
通讯作者:
Luu, Hue H.
Luu, Hue H.
中科院分区:
医学1区
文献类型:
--
作者:
Luther, Gaurav A.;Lamplot, Joseph;Chen, Xiang;Rames, Richard;Wagner, Eric R.;Liu, Xing;Parekh, Akash;Huang, Enyi;Kim, Stephanie H.;Shen, Jikun;Haydon, Rex C.;He, Tong-Chuan;Luu, Hue H.

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骨肉瘤(osteosarcoma,OS)是最常见的原发性骨恶性肿瘤。我们研究了胰岛素样生长因子结合蛋白5(IGFBP 5)结构域在调节OS致瘤性和转移中的作用。N-末端(在较小程度上C-末端)结构域抑制细胞增殖和诱导凋亡,而C-末端结构域抑制细胞迁移和侵袭。连接结构域没有独立的影响。在体内,N-末端结构域降低肿瘤生长而不影响肺转移,而C-末端结构域抑制肿瘤生长和转移。总之,N-和C-末端结构域调节OS致瘤表型,而C-末端结构域抑制OS转移表型。
Osteosarcoma (OS) is the most common primary malignancy of bone. We investigated the roles of insulin-like growth factor binding protein 5 (IGFBP5) domains in modulating OS tumorigenicity and metastasis. The N-terminal (to a lesser extent the C-terminal) domain inhibited cell proliferation and induced apoptosis while the C-terminal domain inhibited cell migration and invasion. The Linker domain had no independent effects. In vivo, the N-terminal domain decreased tumor growth without affecting pulmonary metastases while the C-terminal domain inhibited tumor growth and metastases. In summary, the N- and C-terminal domains modulated OS tumorigenic phenotypes while the C-terminal domain inhibited OS metastatic phenotypes.
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