CXCR6 promotes tumor cell proliferation and metastasis in osteosarcoma through the Akt pathway

Cell Immunol. 2017 Jan:311:80-85. doi: 10.1016/j.cellimm.2016.11.001. Epub 2016 Nov 1.

Abstract

Chemokine (C-X-C motif) receptor 6 (CXCR6) is up-regulated in many malignancies, indicating that CXCR6 plays an important role in tumor progression. However, the expression and function of CXCR6 in osteosarcoma (OS) remains unclear. This study aimed to explore the expression levels and function of CXCR6 in OS tissues and osteosarcoma cell lines MG-63, HOS and U2OS. The protein expression levels of CXCR6 in OS patient tissues and three osteosarcoma cell lines MG-63, HOS and U2OS were assessed. CXCR6-overexpression MG-63 cell lines were established and then the proliferation, invasion and the epithelial-mesenchymal transition (EMT) in those cells were assessed. CXCR6 mRNA levels in OS tissues were significantly higher than those in normal bone tissues. Consistently, both of the mRNA and protein levels of CXCR6 in OS cell lines MG-63, HOS and U2OS were higher than those in normal bone cells hFOB1.19. CXCR6 overexpression not only promoted cell proliferation, invasion and EMT, but also enhanced the phosphorylation of Akt in MG-63 cells. After inhibition of Akt-phosphorylation by Akt inhibitor, LY2940023, CXCR6-induced cell proliferation and invasion were dramatically attenuated. In conclusion, the present study demonstrated that CXCR6 enhances OS cell proliferation and invasion through the Akt pathway.

Keywords: Akt; CXCR6; Invasion; Osteosarcoma; Proliferation.

MeSH terms

  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation
  • Humans
  • Oncogene Protein v-akt / metabolism
  • Osteoblasts / physiology*
  • Osteosarcoma / immunology*
  • Phosphorylation / drug effects
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism

Substances

  • CXCR6 protein, human
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Virus
  • Transforming Growth Factor beta
  • Oncogene Protein v-akt