Endocan as a Biomarker of Endothelial Dysfunction in Cancer

Abstract

Endocan also called endothelial cell-specific-molecule-1 is a product of endothelial cells, highly regulated by vascular endothelial growth factor and expressed during the switch between dormant to fast-growing angiogenic tumors. No other molecule is currently known to be a read out of endothelial activation and dysfunction in tumor progression. We here reviewed the present knowledge about endocan that present clinical value as a tissue-and blood-based prognostic and potentially as a companion biomarker in cancer. By immunohistochemistry endocan was shown to be overexpressed into endothelial cells of small and large vessels in lung, kidney and brain tumors. High endocan serum levels were shown to be significantly correlated with the presence of metastasis and with limited survival in kidney and lung cancers. Moreover, endocan release by endothelial cells was in vitro modulated by addition of anti-angiogenic compounds. At a time where biomarkers are hugely needed to improve anti-angiogenic targeted treatments, endocan could be a pertinent biomarker to select patients and/or to clinically monitor the efficacy of cancer drugs. Through its awaited functional applications, endocan appears today as a promising biomarker to access to personalized medicine and to optimize therapy cost / benefit ratio.

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

“…The release of Endocan by cultured endothelial cells has been largely described to be strongly upregulated in presence of proangiogenic molecules such as VEGF, FGF-2, and VEGF-C that are critical mediators involved in angiogenesis (i.e., formation of blood vessel), lymphangiogenesis (i.e., formation of lymphatic vessel), and cancer progression (spreading and metastasis) [23, 28, 35, 36, 39, 66]. In addition, Endocan has been shown to directly promote the mitogenic and migratory activities of VEGF-A and -C on cultured endothelial cells [66].…”

“…Since then, Endocan has rapidly emerged as a very distinctive PG, in many aspects: (i) Endocan is the one of very few circulating PG sensu stricto , (ii) in contrast with most ECM PGs, which are usually large, modular proteins that harbor several GAG chains, Endocan comprises a relatively small polypeptide associated to one single polysaccharide chain, and (iii) characterization of Endocan DS chain revealed uncommon structural features and saccharide composition [22]. Interestingly, increasing experimental evidence has reported that Endocan is overexpressed in cancer, sepsis, obesity, or inflammatory conditions [20, 21, 23–28]. Furthermore, blood levels of freely circulating PG have been associated with poor prognosis in several types of cancers (reviewed in [28]).…”

“…Interestingly, increasing experimental evidence has reported that Endocan is overexpressed in cancer, sepsis, obesity, or inflammatory conditions [20, 21, 23–28]. Furthermore, blood levels of freely circulating PG have been associated with poor prognosis in several types of cancers (reviewed in [28]). The aim of this paper is to review the present knowledge about Endocan expression, structure, and activity, with a special focus on the recent developments that have been highlighting that Endocan, as an endothelial proteoglycan not only is a biomarker of neoangiogenesis but also appears today as a signature of the tumor progression when it is expressed by the tumor cells themselves.…”

Role of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD)

“…It is thought that this aberrant vessel plexus gives immune protection to developing malignant cells by preventing egress and local activity of natural killer (NK) cells [13,14]. Fibroblasts originated from type-3 EMT are designated as “cancer-associated fibroblasts” [15].…”

Endocan: A novel inflammatory indicator in cardiovascular disease?

“…Recently, endocan was reported to dose-dependently inhibit migration in transmigration endothelial assays of NK cells that reside naturally in the vasculature. [10] M A N U S C R I P T…”