Notably, this was due to cancer cell release of VEGF ligands binding to VEGFR1 on sensory afferent fibers, as sensory neuron-specific deletion of VEGFR1 and pharmacological blockade of VEGFR1/VEGF signaling suppressed cancer pain and attenuated peripheral nerve sprouting into the tumor stroma.74 In addition, bone cancer cells also sensitize nerve fibers and induce peripheral sprouting through the release of granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), whose receptors are present on local peripheral nociceptor afferents. This evidence concerns the gene CSF3 and bone cancer.