New insights into the molecular control of the lymphatic vascular system and its role in disease

Abstract

The cutaneous lymphatic system plays an important role in the maintenance of tissue fluid homeostasis, in the afferent phase of the immune response, and in the metastatic spread of skin cancers. However, the lymphatic system has not received as much scientific attention as the blood vascular system, largely due to a lack of lymphatic-specific markers and to the dearth of knowledge about the molecular regulation of its development and function. The recent identification of genes that specifically control lymphatic development and the growth of lymphatic vessels (lymphangiogenesis), together with the discovery of new lymphatic endothelium-specific markers, have now provided new insights into the molecular mechanisms that control lymphatic growth and function. Moreover, studies of several genetic mouse models have set the framework for a new molecular model for embryonic lymphatic vascular development, and have identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. These scientific advances have also provided surprising evidence that malignant tumors can directly promote lymphangiogenesis and lymphatic metastasis, and that lymphatic vessels play a major role in cutaneous inflammation and in the cutaneous response to UVB irradiation.