Endocan in Cancers: A Lesson from a Circulating Dermatan Sulfate Proteoglycan

Abstract

As most proteoglycans exert their biological activities in the pericellular region, circulating Endocan has appeared since its discovery as an atypical dermatan sulfate proteoglycan, with distinctive structural and functional properties. Endocan is naturally expressed by endothelial cells, highly regulated in presence of proinflammatory and proangiogenic molecules, binds to matrix proteins, growth factors, integrin, and cells, and may be then considered as an accurate marker of endothelial activation. Consequently, Endocan expression has been associated with a growing number of pathological conditions where endothelium gets challenged and notably in highly vascularized cancers. In this context, Endocan has indeed been rapidly emerging as a promising tissue- and blood-based marker of the vascular growth and neoangiogenesis during cancer progression. Furthermore, very recent studies have reported an expression of Endocan by the tumor cells themselves. This highlights Endocan as a multifaceted molecule with a great interest for researchers and clinicians to better understand tumor development, from the bench to the clinics. With promising perspectives of clinical applications, Endocan thus appears as an exciting model for on going and future developments of proteoglycan-based approaches in cancer diagnostics and/or therapy.

Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient Hereditary Angioedema

“…A newly proposed endothelial marker, endocan, was found to be correlated with vascular inflammatory responses in various conditions, such as sepsis, cancer, and even atherosclerosis [17,18,19,20]. In a recent, comprehensive study, Lee et al [14] demonstrated that endocan elicits proinflammatory responses, such as hyperpermeability, cytoskeleton rearrangement, upregulation of the cellular adhesion molecule expression, leukocyte adhesion and migration via interaction with mitogen-activated protein kinase, signaling pathways, and NF-kB.…”

Diagnostic Significance of Measuring Vascular Endothelial Growth Factor for the Differentiation between Malignant and Tuberculous Pleural Effusion

“…Although the exact regulatory mechanism of endocan production is not well established, recent studies suggest that a number of signaling pathways and bioactive mediators are involved. The expression of endocan is upregulated by VEGF-A, VEGF-C, tumor necrosis factor-α, and transforming growth factor-β1 (Lassalle et al 1996;Rennel et al 2007;Maurage et al 2009;Delehedde et al 2013). Because of these relations between endocan and VEGF, we compared the diagnostic efficiencies of VEGF and endocan with carcinoembryonic antigen (the tumor marker that currently provides the best diagnostic accuracy (Shi et al 2008) and CYFRA.…”

Highlight on Mouse Endocan

“…4 It belongs to a set of 6 genes specifically overexpressed during the angiogenic switch. 5 In human tumors, endocan is overexpressed by endothelial cells from various cancers such as non-small lung cancer, hepatocarcinoma, kidney cancer, glioblastoma, and bladder cancer. 5 Multiple studies identified endocan expression as part of molecular signatures defining a poor prognosis in non-small lung cancer, breast cancer, glioblastoma, and hepatocarcinoma.…”

“…5 In human tumors, endocan is overexpressed by endothelial cells from various cancers such as non-small lung cancer, hepatocarcinoma, kidney cancer, glioblastoma, and bladder cancer. 5 Multiple studies identified endocan expression as part of molecular signatures defining a poor prognosis in non-small lung cancer, breast cancer, glioblastoma, and hepatocarcinoma. 5 In mice models of tumor xenografts, overexpression of human endocan induces tumor growth of nontumorigenic HEK293 (human embryonic kidney) cells and accelerate tumor growth of the tumorigenic HT-29 cells.…”

“…5 Multiple studies identified endocan expression as part of molecular signatures defining a poor prognosis in non-small lung cancer, breast cancer, glioblastoma, and hepatocarcinoma. 5 In mice models of tumor xenografts, overexpression of human endocan induces tumor growth of nontumorigenic HEK293 (human embryonic kidney) cells and accelerate tumor growth of the tumorigenic HT-29 cells. 6 Most of these effects have been attributed to the glycan moiety of endocan.…”