Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway

Oncol Rep. 2016 Oct;36(4):2275-81. doi: 10.3892/or.2016.5045. Epub 2016 Aug 25.

Abstract

Angiogenesis is essential for tumor growth, especially in hepatocellular carcinoma (HCC). The hypervascularity is associated with poor prognosis and highly invasive HCC. The C‑X‑C chemokine receptor type 7 (CXCR7) has been implied overexpressed in many tumor types. Our study aimed to investigate the CXCR7 function in HCC. The tube formation, Transwell migration assay of human umbilical vein endothelial cells (HUVECs) and chicken chorioallantoic membrane (CAM) assay were used. We confirmed that CXCR7 induces angiogenic capacity. Moreover, overexpressing CXCR7 increased the phosphorylated (but not total) AKT expression in HCC cells. Furthermore, overexpressing CXCR7 increased the expression of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑8 in HCC cells. Additionally, inhibition of AKT by LY294002 abrogated CXCR7‑induced angiogenic capacity in HCC cells. Our study suggested that CXCR7 plays an important pro‑angiogenic role in HCC via activation of the AKT pathway. So CXCR7 may be a potential target for anti‑angiogenic therapy in HCC.

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Receptors, CXCR / biosynthesis
  • Receptors, CXCR / genetics*
  • Signal Transduction / genetics

Substances

  • ACKR3 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Receptors, CXCR
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt