Pressing the right buttons: Signaling in lymphangiogenesis

Abstract

Lymphatic vasculature is increasingly recognized as an important factor both in the regulation of normal tissue homeostasis and immune response and in many diseases, such as inflammation, cancer, obesity, and hypertension. In the last few years, in addition to the central role of vascular endothelial growth factor (VEGF)-C/VEGF receptor-3 signaling in lymphangiogenesis, significant new insights were obtained about Notch, transforming growth factor β/bone morphogenetic protein, Ras, mitogen-activatedproteinkinase,phosphatidylinositol 3 kinase, and Ca2+/calcineurin signaling pathways in the control of growth and remodeling of lymphatic vessels. An emerging picture of lymphangiogenic signalingis complex andinmanywaysdistinct from the regulation of angiogenesis. This complexity provides new challenges, but also new opportunities for selective therapeutic targeting of lymphatic vasculature. © 2014 by The American Society of Hematology.