A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain

Cancer Cell. 2015 Jun 8;27(6):780-96. doi: 10.1016/j.ccell.2015.04.017.

Abstract

Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Pain / drug therapy
  • Pain / metabolism*
  • Pain / pathology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • Sensory Receptor Cells / pathology
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis*

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor Receptor-1