Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial

S Soker1, S Takashima, H Q Miao

  • 1Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Cell
|April 7, 1998
PubMed

Insights

Neuropilin-1 acts as a third vascular endothelial growth factor (VEGF) receptor, specifically binding VEGF165. This interaction enhances VEGF165 binding to KDR, modulating angiogenesis and endothelial cell activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Vascular endothelial growth factor (VEGF) is crucial for angiogenesis, primarily signaling through KDR/Flk-1 and Flt-1 receptors.
  • Tumor cells express various growth factor receptors, influencing tumor growth and metastasis.

Purpose of the Study:

  • To identify and characterize novel receptors for VEGF.
  • To investigate the role of a newly identified VEGF receptor in angiogenesis.

Main Methods:

  • Purification and expression cloning of a novel VEGF receptor from tumor cells.
  • Coexpression studies with KDR to assess binding and functional activity.
  • Inhibition assays to determine the role of neuropilin-1 in VEGF signaling.

Main Results:

  • A third VEGF receptor, binding VEGF165 but not VEGF121, was identified and cloned.
  • This receptor was found to be identical to human neuropilin-1.
  • Neuropilin-1 enhanced VEGF165 binding to KDR and VEGF165-mediated chemotaxis.
  • Inhibiting neuropilin-1 binding reduced VEGF165's mitogenic activity on endothelial cells.

Conclusions:

  • Neuropilin-1 functions as a novel VEGF receptor, modulating VEGF165 binding to KDR.
  • Neuropilin-1 plays a significant role in regulating VEGF-induced angiogenesis and endothelial cell function.

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