IGFBP-3 stimulates human osteosarcoma cell migration by upregulating VCAM-1 expression.

Abstract

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.

• Authors: Chia-Chia Chao, Wei-Fang Lee, Wei-Hung Yang, Chih-Yang Lin, Chien-Kuo Han, Yuan-Li Huang, Yi-Chin Fong, Min-Huan Wu, I-Ta Lee, Yuan-Hsin Tsai, Chih-Hsin Tang, Ju-Fang Liu
• Journal: Life sciences (Life Sci) Vol. 265 Pg. 118758 (Jan 15 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33188835 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• IGFBP3 protein, human
• Insulin-Like Growth Factor Binding Protein 3
• Vascular Cell Adhesion Molecule-1

Topics

• Blotting, Western
• Bone Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Fluorescent Antibody Technique
• Gene Expression Regulation, Neoplastic
• Humans
• Insulin-Like Growth Factor Binding Protein 3 (metabolism, physiology)
• Osteosarcoma (metabolism)
• Up-Regulation
• Vascular Cell Adhesion Molecule-1 (metabolism)