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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article number118758
JournalLife Sciences
Volume265
DOIs
Publication statusPublished - Jan 15 2021

Keywords

  • IGFBP-3
  • Metastasis
  • Migration
  • Osteosarcoma
  • VCAM-1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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