KDR and neoplasm: Conversely, PIGF can also directly induce angiogenesis through regulation of the crosstalk between VEGFR-1 and VEGFR-2, amplification of the VEGF-A signal through VEGFR-2 activation, enhancement of the angiogenic signal through the activation of the VEGFR-1/VEGFR-2 heterodimers via VEGF/PlGF heterodimers, impairment of dendritic cell maturation leading to immune suppression and promotion of the metastatic process by recruiting pro-angiogenic progenitor cells from the bone marrow to the tumor and the pre-metastatic niche, with consequent proliferation of metastatic cells (23–25).