Amphiregulin enhances intercellular adhesion molecule-1 expression and promotes tumor metastasis in human osteosarcoma

Oncotarget. 2015 Dec 1;6(38):40880-95. doi: 10.18632/oncotarget.5679.

Abstract

Osteosarcoma is a common, high malignant, and metastatic bone cancer. Amphiregulin (AREG) has been associated with cancer cellular activities. However, the effect of AREG on metastasis activity in human osteosarcoma cells has yet to be determined. We determined that AREG increases the expression of intercellular adhesion molecule-1 (ICAM-1) through PI3K/Akt signaling pathway via its interaction with the epidermal growth factor receptor, thus resulting in the enhanced cell migration of osteosarcoma. Furthermore, AREG stimulation increased the association of NF-κB to ICAM-1 promoter which then up-regulated ICAM-1 expression. Finally, we observed that shRNA silencing of AREG decreased osteosarcoma metastasis in vivo. Our findings revealed a relationship between osteosarcoma metastatic potential and AREG expression and the modulating effect of AREG on ICAM-1 expression.

Keywords: EGFR; ICAM-1; amphiregulin; cell migration; osteosarcoma metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphiregulin
  • Animals
  • Apoptosis
  • Blotting, Western
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • EGF Family of Proteins / genetics
  • EGF Family of Proteins / metabolism*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, SCID
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • AREG protein, human
  • Amphiregulin
  • EGF Family of Proteins
  • ICAM1 protein, human
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • Intercellular Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases
  • EGFR protein, human
  • ErbB Receptors