Endocan is a proteoglycan produced specifically by the vascular endothelium.
Also called Endothelial cell Specific Molecule (or ESM-1), it is encoded by a single non-polymorphic gene called esm1. Its synthesis and secretion are increased by proinflammatory cytokines such as TNF or IL-1, and by angiogenic factors such as VEGF or FGF-2. Conversely, endocan expression is inhibited by activation of the endothelial PI3K pathway induced by a variety of mediators such as gamma interferon or insulin.
Biological properties
Endocan has 2 major biological properties: anti-inflammatory and pro-angiogenic.
Anti-inflammatory property of endocan: PubMed studies
Endocan exhibits anti-inflammatory activity, acting as an inhibitor of the LFA-1 leukocyte integrin-dependent activation cascade. By preventing leukocyte entry into interstitial tissue, endocan reduces inflammation in vitro in models of transendothelial leukocyte migration, and in vivo in models of experimental ARDS (PubMed).
This biological property may explain why endocan is expressed primarily in the lungs and more incidentally in the kidney: either in the most perfused organs which require greater anti-inflammatory control.
Endocan proangiogenic property: PubMed studies
Endocan is particularly overexpressed by the highly specialized endothelial cells that form the vascular bud (Strasser et al. 2010 ; Del Toro et al. 2010 ; Recchia et al. 2010).
Endocan participates in physiological and tumor angiogenesis in close association with VEGF. Their joint presence promotes endothelial migration in models of endothelial damage / repair in vitro and in animals in models of retinal hypoxia and tumor.
The causal relationship between endocan and cancer was suggested early on on the basis of its role in angiogenesis. It is suggested that endocan could increase both angiogenesis and the proliferation of tumor cells themselves through interactions between growth factors and endocan glycan (PubMed studies). There is also some evidence to believe that this protumoral action is indirect, preventing the inflammatory stromal reaction from taking hold (PubMed studies).
La relation de causalité entre endocan et cancer a été très tôt suggérée sur la base de son rôle dans l’angiogenèse. On peut penser qu’endocan, pourrait augmenter à la fois l’angiogenèse et la prolifération des cellules tumorales elles-mêmes au travers les interactions entre des facteurs de croissance et le glycane d’endocan (PubMed studies). Il y a aussi des éléments pour penser que cette action protumorale soit indirecte, en empêchant la réaction inflammatoire stromale de s’installer (PubMed studies).