IGFBP-3 stimulates human osteosarcoma cell migration by upregulating VCAM-1 expression
Chia-Chia Chao1, Wei-Fang Lee2, Wei-Hung Yang3
1Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan.
Aims:
Insulin-like growth factor (IGF) signaling has been documented in several human malignancies and is thought to contribute to cellular differentiation and migration, as well as malignant progression. A major binding molecule of IGF, IGF-binding protein 3 (IGFBP-3), regulates multiple IGF effects. Here, we focused on the effect of IGFBP-3 in the motility of osteosarcoma cells and examined signaling regulation.
Materials And Methods:
Using a human osteosarcoma tissue array, immunohistochemical staining determined levels of IGFBP-3 expression in osteosarcoma tissue and in normal tissue. The wound healing migration assay, Transwell migration assay, luciferase reporter assay, immunofluorescence staining, Western blot and real-time quantitative PCR were performed to examine whether IGFBP-3 facilitates VCAM-1-dependent migration of osteosarcoma cells.
Key Findings:
In this study, we found significantly higher IGFBP-3 levels in osteosarcoma tissue compared with normal healthy tissue. IGFBP-3 treatment of two human osteosarcoma cell lines promoted cell migration and upregulated levels of VCAM-1 expression via PI3K/Akt and AP-1 signaling.
Significance:
IGFBP-3 appears to be a novel therapeutic target in metastatic osteosarcoma.
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