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

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...

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Published inCancer letters Vol. 336; no. 1; pp. 222 - 230
Main Authors 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
Format Journal Article
LanguageEnglish
Published Ireland Elsevier Ireland Ltd 09.08.2013
Elsevier Limited
Subjects
Adenoviruses
Animal model
Animals
Apoptosis
Bone Neoplasms - metabolism
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell Movement
Cell Proliferation
Extracellular matrix
Gene Expression Regulation, Neoplastic
HEK293 Cells
Hematology, Oncology and Palliative Medicine
Humans
Hydroxyapatite
IGFBP5
Insulin-like growth factor binding protein
Insulin-Like Growth Factor Binding Protein 5 - metabolism
Insulin-like growth factors
Metastasis
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Osteosarcoma
Osteosarcoma - metabolism
Pathogenesis
Phenotype
Protein Interaction Domains and Motifs
Proteins
Time Factors
Animal model
Metastasis
IGFBP5
Insulin-like growth factor binding protein
Osteosarcoma
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.05.002