Table 1.

The molecular hallmarks of the lymphatic endothelium.

The Markers of the Lymphatic Endothelium	The Functional Characteristics of Proteins Expressed in the Lymphatic Endothelium
LYVE-1—Lymphatic vessel endothelial hyaluronan receptor 1	Hyaluronan (HA) is an element of skin and mesenchymal tissues that regulates cell migration in the course of wound healing, inflammation, and embryonic morphogenesis [50]. LYVE-1 is a specific transmembrane receptor of HA, which was first described by Banerji in 1999 [51]. LYVE-1 was found primarily on both the luminal and abluminal surface of lymphatic endothelial cells [51,52]. The functional role of LYVE-1 is still the subject of debate, but there are evidences that LYVE-1 plays an important role in hyaluronan transport and turnover, or in hyaluronan localization to the surface of lymphatic endothelium providing for migration CD44+ leukocytes or tumor cells [53]. Notice, there are some findings where expression of Lyve-1 was also observed in the human iliac atherosclerotic arteries [54], in the embryonic blood vessels [55], in macrophages [56], the reticulo-endothelial system [48]. Therefore, the specificity of Lyve-1 as a marker for the lymphatic vessels is not strong enough.
Prox1—Prospero homeobox protein 1	Transcription factor regulating the process of growth and differentiation of endothelial cells of lymphatic vessels [57]
CCL21-Chemokine (C-C motif ligand 21)	It is secreted by endothelial cells of lymphatic vessels and is involved in activation of T-lymphocyte movement, migration of lymphocytes to other organs, and dendritic cells into lymph nodes [58].
VEGFR3—Vascular endothelial growth factor receptor 3	VEGFR3 is a receptor that triggers the lymphangiogenesis, i.e., the formation of new lymphatic vessels [59]. In transgenic mice with absence of VEGFR3 gene, the meningeal lymphatic vessels do not develop, and lymph node hypoplasia is noted [21].
PDPN—Podoplanin	PDPN is integral membrane protein, which is responsible for the normal development of the network of lymphatic vessels, providing drainage of the intercellular fluid. If the synthesis is broken, lymphedema is formed [60]. The PDPN activation is accompanied by lymphangiogenesis, which is regarded as an important indicator of tumor growth [61].
ITGA9—Integrin-α9	ITGA9 is a protein, which is a part of the valves in the lymphatic vessels [62].