Endothelial cell-specific molecule–1 (ESM-1)—so-called endocan—is a novel endothelium derived soluble dermatan sulfate proteoglycan (PG) that is constitutively expressed by endothelial cells in lungs and kidneys and can be detected in human blood. It is encoded by the ESM1 gene. The expression of this gene is regulated by several cytokines and growth factors, such as vascular endothelial growth factor. Inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, stimulate the upregulation of endocan mRNA and the secretion of endocan from endothelial cells. The binding of circulating endocan to leukocyte ligand for ICAM-1—Lymphocyte Function-associated Antigen-1 (LFA-1) and to leukocyte ligand for VCAM-1—Very Late Antigen-4 (VLA-4) is important in leukocyte adhesion and interaction with activated endothelium. Endocan is a key player in the regulation of major processes such as cell adhesion in inflammatory disorders and tumor progression.
ESM1 is a secreted protein which is produced by adipocytes. It has been noticed that ESM1 may play some role in obesity-associated vascular disease since circulating ESM-1 levels are reduced in the overweight and obese. ESM1 is mainly expressed in the endothelial cells in human lung and kidney tissues. The expression of ESM1 gene is regulated by cytokines, suggesting that it may play a role in endothelium-dependent pathological disorders. Recently, ESM1 has been described as a specific biomarker of tip cells during neoangiogenesis. Its expression has been shown to be increase in presence of pro-angiogenic growth factors such as VEGF or FGF-2. In hypervascularized cancers, overexpression of endocan has been detected by immunohistochemistry using monoclonal antibodies against ESM1.
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