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

  • Author(s): Selvaraj, Deepitha
  • Gangadharan, Vijayan
  • Michalski, Christoph W
  • Kurejova, Martina
  • Stösser, Sebastian
  • Srivastava, Kshitij
  • Schweizerhof, Matthias
  • Waltenberger, Johannes
  • Ferrara, Napoleone
  • Heppenstall, Paul
  • Shibuya, Masabumi
  • Augustin, Hellmut G
  • Kuner, Rohini
  • et al.
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.

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