NR2F2 regulates bone marrow-derived mesenchymal stem cell-promoted proliferation of Reh cells

Mol Med Rep. 2016 Aug;14(2):1351-6. doi: 10.3892/mmr.2016.5389. Epub 2016 Jun 10.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are pivotal components of the leukemic microenvironment. BM-MSCs have been previously reported to promote the proliferation of leukemic cells. To further understand the molecular mechanisms of BM-MSC-induced proliferation of leukemic cells, the present study co-cultured acute lymphoblastic leukemia (ALL) Reh cells with BM-MSCs. The current study used methods including shRNA, flow cytometry, MTT, reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting. The data of the present study demonstrated that BM‑MSCs promote the proliferation of Reh cells and the NR2F2 mRNA and protein levels were elevated in BM‑MSCs following co‑culture. Additionally, it was demonstrated that shRNA knockdown of NR2F2 inhibited BM‑MSC‑induced proliferation of Reh cells. Furthermore, following downregulation of NR2F2, vascular endothelial growth factor A (VEGFA) secretion by BM‑MSCs was reduced. The present study demonstrated that NR2F2 mediates BM‑MSC‑induced proliferation of Reh cells, partially via regulation of VEGFA. Disrupting microenvironmental support by targeting NR2F2 may be a potential therapeutic strategy for ALL.

MeSH terms

  • Apoptosis / genetics
  • COUP Transcription Factor II / genetics*
  • COUP Transcription Factor II / metabolism
  • Cell Communication*
  • Cell Cycle / genetics
  • Cell Differentiation / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Coculture Techniques
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • COUP Transcription Factor II
  • NR2F2 protein, human
  • Vascular Endothelial Growth Factor A