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

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• 作者：Gaurav A. Luther^a ; Joseph Lamplot^a ; Xiang Chen^a ; ^b ; Richard Rames^a ; Eric R. Wagner^a ; Xing Liu^a ; ^c ; ^d ; Akash Parekh^a ; Enyi Huang^a ; ^e ; Stephanie H. Kim^a ; Jikun Shen^a ; Rex C. Haydon^a ; Tong-Chuan He^a ; ^c ; Hue H. Luu^a ; ^{hluu@surgery.bsd.uchicago.edu}
• 关键词：IGFBP5 ; Insulin-like growth factor binding protein ; Osteosarcoma ; Animal model ; Metastasis
• 刊名：Cancer Letters
• 出版年：2013
• 出版时间：9 August, 2013
• 年：2013
• 卷：336
• 期：1
• 页码：222-230
• 全文大小：2744 K

文摘

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.