title: 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 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.
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Gaurav A
authors.initials: GA
authors.lastname: Luther
authors.forename: Joseph
authors.initials: J
authors.lastname: Lamplot
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Rames
authors.forename: Eric R
authors.initials: ER
authors.lastname: Wagner
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Akash
authors.initials: A
authors.lastname: Parekh
authors.forename: Enyi
authors.initials: E
authors.lastname: Huang
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000378:metabolism*; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs; D013997:Time Factors
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5