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A novel function for dendritic cell: clearance of VEGF via VEGF receptor-1

Yi Xie1, Jianqing Fan, Juhua Chen

  • 1Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.

Biochemical and Biophysical Research Communications
|January 27, 2009
PubMed

Insights

Dendritic cells (DCs) internalize vascular endothelial growth factor (VEGF) during immunotherapy, reducing its levels outside the cell. This novel DC function clarifies the mechanism behind VEGF decrease in cancer patients undergoing DC-based treatments.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Biology

Background:

  • Plasma levels of vascular endothelial growth factor (VEGF) decrease during dendritic cell (DC)-based immunotherapy in tumor patients.
  • The underlying mechanism for this VEGF reduction remains unclear.

Purpose of the Study:

  • To investigate the interaction between dendritic cells (DCs) and VEGF.
  • To elucidate the mechanism by which DCs affect VEGF levels during immunotherapy.

Main Methods:

  • Incubation of DCs with recombinant human VEGF (rhVEGF) or tumor-conditioned medium (TCM).
  • Measurement of intracellular and supernatant VEGF levels.
  • Assessment of VEGF mRNA expression in DCs.
  • Tracking of Cy3-labeled VEGF internalization by DCs.
  • Inhibition studies using anti-VEGF receptor-1 (Flt-1) antibodies and endocytosis inhibitors (CCCP, genistein).

Main Results:

  • VEGF levels decreased in DC supernatants, while intracellular VEGF increased.
  • Exogenous VEGF suppressed endogenous VEGF mRNA expression in DCs, indicating it's not de novo synthesis.
  • DCs efficiently and specifically internalized exogenous VEGF.
  • VEGF internalization by DCs was inhibited by anti-Flt-1 antibodies and endocytosis inhibitors.

Conclusions:

  • Dendritic cells possess a novel function of actively internalizing VEGF.
  • This internalization mechanism, dependent on VEGF receptor-1 and endocytosis, contributes to the observed decrease in plasma VEGF levels during DC-based immunotherapy.
  • Understanding this DC-VEGF interaction provides insights into immunotherapy efficacy.

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