The 786-0 renal cancer cell-derived exosomes promote angiogenesis by downregulating the expression of hepatocyte cell adhesion molecule

Mol Med Rep. 2013 Jul;8(1):272-6. doi: 10.3892/mmr.2013.1458. Epub 2013 May 8.

Abstract

The aims of the current study were to determine whether 786‑0 renal cancer cell‑derived exosomes promote human umbilical vein endothelial cells (HUVECs) to form tubular structures and to uncover the underlying mechanisms associated with this process. Exosomes were extracted and purified using ultrafiltration and sucrose gradient centrifugation and characterized by transmission electron microscopy. Tubular structure formation was observed using the matrigel tubular assay. In addition, an adenovirus vector was used to transfect the hepatocyte cell adhesion molecule (hepaCAM) gene into renal cancer 786‑0 cells. The expression of hepaCAM and vascular endothelial growth factor (VEGF) mRNA and protein was determined by reverse transcription‑polymerase chain reaction and western blot analysis, respectively. Tumor cell‑derived exosomes were observed to significantly increase tubular formation in HUVECs. Following transfection with the hepaCAM gene, VEGF expression in 786‑0 cells was markedly decreased. In HUVECs, exosome treatment increased VEGF mRNA and protein expression, while hepaCAM expression was only decreased at the protein level. In the present study, renal cancer 786‑0 cell‑derived exosomes significantly promoted angiogenesis via upregulation of VEGF expression in HUVECs, which may be induced by the downregulation of hepaCAM.

MeSH terms

  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Exosomes / metabolism*
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Neovascularization, Pathologic / metabolism*
  • Proteins / genetics*
  • Proteins / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cell Cycle Proteins
  • HEPACAM protein, human
  • Proteins
  • Vascular Endothelial Growth Factor A