Figure 2 | Mode of action of lymphangiogenic growth factors.   The lymphangiogenic growth factors vascular endothelial growth factor-C (VEGFC) and VEGFD are produced by a range of cells and tissues during embryogenesis, adult life and certain pathologies, including cancer. The full-length growth factors are processed by as yet uncharacterized proteases that cleave the amino- and carboxy-terminal propeptides (light blue and red L-shapes, respectively) from the VEGF homology domain (VHD) to generate a mature form that consists of dimers of the VHD (purple oval) that bind the receptors VEGFR2 and VEGFR3 with high affinity. In the case of VEGFD, the mature form has a 290-fold and 40-fold greater affinity for VEGFR2 and VEGFR3, respectively, than the unprocessed form³³. Activation of VEGFR3 induces lymphangiogenesis, whereas activation of VEGFR2 is thought to drive angiogenesis.

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