Back to Search
Start Over
Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma.
Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma.
- Source :
-
Oncogene [Oncogene] 2011 Sep 15; Vol. 30 (37), pp. 3907-17. Date of Electronic Publication: 2011 Apr 04. - Publication Year :
- 2011
-
Abstract
- Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.
- Subjects :
- Adolescent
Adult
Animals
Apoptosis
Bone Neoplasms genetics
Bone Neoplasms pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Child
Down-Regulation
Female
Gene Expression Profiling
Gene Knockdown Techniques
Humans
Insulin-Like Growth Factor Binding Protein 5 genetics
Lung Neoplasms genetics
Lung Neoplasms secondary
Male
Mice
Mice, Nude
Osteosarcoma genetics
Osteosarcoma secondary
Young Adult
Bone Neoplasms metabolism
Insulin-Like Growth Factor Binding Protein 5 metabolism
Lung Neoplasms metabolism
Osteosarcoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 30
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 21460855
- Full Text :
- https://doi.org/10.1038/onc.2011.97