Morphogenesis, structure and properties of lymphatic vessels

In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth factors and/or as modulators playing a role in vessel caliber regulation during lymphangiogenesis. We discuss the most important diseases of the lymphatic system, their molecular basis and tumors derived from lymphatic vessels.