Molecular regulation mechanisms of lymphangiogenesis

Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and growth factors for lymphangiogenesis. Importantly, lymphatic endothelial receptor tyrosine kinase VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype. It demonstrates the plasticity of endothelial cells and offers the possibility of transcriptional reprogramming of vascular endothelial cells as future putative therapeutic applications.