Lymphatics at the crossroads of angiogenesis and lymphangiogenesis
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bar Medical School, Italy.
The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described.PubMed
Molecular lymphangiogenesis: new players.
Tammela T, Petrova TV, Alitalo K.
Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Helsinki University Central Hospital, POB 63 (Haartmaninkatu 8), 00014 University of Helsinki, Helsinki, Finland.
The function of the lymphatic vascular system as a conduit for immune cells and excess tissue fluid has been known for over a century, but the molecular players involved in lymphangiogenesis--the formation of lymphatic vessels--have remained unknown until recently. Signals mediated by vascular endothelial growth factor-C, the homeodomain transcription factor PROX1 and the forkhead transcription factor FOXC2 have been implicated in the growth, morphogenesis and hierarchic organization of the lymphatic vascular network. Recent results have also shown the importance of the angiopoietin-Tie and ephrin-Eph signaling systems in lymphangiogenesis, suggesting that these pathways regulate the lymphatic vascular system in a manner similar to, yet distinct from, their regulation of angiogenesis. This review provides an overview of the molecular players involved in lymphangiogenesis, with special emphasis on recently discovered molecular mechanisms