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

Autor: Yi-Chin Fong, Chien-Kuo Han, Chih-Yang Lin, Chia-Chia Chao, Wei-Fang Lee, I-Ta Lee, Wei-Hung Yang, Min-Huan Wu, Yuan-Hsin Tsai, Yuan-Li Huang, Ju-Fang Liu, Chih-Hsin Tang
Rok vydání: 2020
Předmět:
Zdroj: Life sciences. 265
ISSN: 1879-0631
Popis: 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.
Databáze: OpenAIRE