While active angiogenesis is known to be a prerequisite for tumor growth beyond a few mm3 in size, lymphangiogenesis in normal or pathological adult tissues, including malignant tumors has not been reported. If lymphangiogenesis takes place during cancer progression, cancers with active lymphangiogenesis could be predisposed to metastatic spread via the lymphatic system and thus to poor survival.
VEGFR-3 is a receptor tyrosine kinase that is similar to the two VEGF receptors in structure but does not bind VEGF, placenta growth factor, or VEGF-B. VEGFR-3 is initially expressed in all embryonic endothelia, but its expression in the blood vessel endothelium decreases during development, and it becomes largely restricted to the lymphatic endothelium in adult tissues.
The two known ligands of VEGFR-3 have a high degree of homology to VEGF and have been named as VEGF-C17 and VEGF-D18. Experiments in transgenic mice have shown that VEGF-C is a growth factor for the developing lymphatic vessels and expression of VEGF-C mRNA has also been detected in malignant human tumors.