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IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma |
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| Authors: | Gaurav A. Luther Joseph Lamplot Xiang Chen Richard Rames Eric R. Wagner Xing Liu Akash Parekh Enyi Huang Stephanie H. Kim Jikun Shen Rex C. Haydon Tong-Chuan He Hue H. Luu |
| Affiliation: | 1. Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA;2. Department of Orthopaedic Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi’an, China;3. The Stem Cell Biology and Therapy Laboratory, The Children’s Hospital of Chongqing Medical University, Chongqing, China;4. Department of Pediatric Orthopaedics, The Children’s Hospital of Chongqing Medical University, Chongqing, China;5. Chongqing key Laboratory for Oral Diseases and Biomedical Sciences, The Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, China |
| Abstract: | 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. |
| Keywords: | IGFBP5 Insulin-like growth factor binding protein Osteosarcoma Animal model Metastasis |
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