Disease relevance of ESM1

• ESM-1 also called endocan, is overexpressed in hypervascularized cancers [1]
• In lung cancers, endocan / ESM-1 was shown to be overpressed in tissues sections by immunohistochemistry and in blood using a sandwich ELISA. Endocan appears as a prognostic biomarker in lung cancers [2]
• Vascular endocan / ESM-1 is markedly overexpressed in renal cell carcinoma [3]. High levels of blood endocan / ESM-1 measured by ELISA were observed in patients suffering from renal clear cell carcinoma carcinoma.
• Using monoclonal antibodies against endocan and by immunohistochemistry, Endocan / ESM-1 was shown to be overexpressed in high grade glioma [4]. Low grade glioma does not express vascular endocan.
• Endocan / ESM-1 is overexpressed in gastric cancers [5]
• As obesity is related to systemic inflammation (examplified by increased circulating levels of C-reactive protein and interleukin-6), the formation of ESM-1 in adipocytes and its activation by protein kinase C may play a role in the regulation of inflammatory processes [6].
• Moreover, ESM-1 was detected in the serum of healthy subjects at an average concentration of 1.08 ng/ml, and we demonstrated that the serum level of ESM-1 is dramatically increased in patients presenting a septic shock [7].
• Endocan or endothelial cell-specific molecule-1: a novel prognostic marker of sepsis [8]
• Circulating ESM-1 levels are reduced in the overweight and obese, consistent with the notion that ESM-1 may play some role in obesity-associated vascular disease [9].

High impact information on ESM1

• Endocan also called endothelial cell-specific molecule-1 is a dermatan sulfate proteoglycan of 50 kDa, freely circulating in blood and secreting by human endothelial cells [10]
• Endocan / ESM-1 binds HGF / SF, a pro-angiogenic molecule through its dermatan sulfate chain [10]
• Endocan / ESM-1 is a biomarker of tip cells as observed in neoangiogenesis [11]

Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1 [12].

• ESM-1 consistently inhibited the specific binding of soluble ICAM-1 to Jurkat cells in a dose-dependent manner [12].
• We previously showed that endothelial cell specific molecule-1 (ESM-1) is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines [12].

Biological context of ESM1

• Endocan / ESM-1 expression is upregulated in presence of pro-angiogenic vascular endothelial growth factor (VEGF) [1]
• Constitutive ESM-1 gene expression was shown to be tissue-restricted to the human lung [13].
• A time-dependent up-regulation of ESM-1 mRNA was seen after addition of tumor necrosis factor alpha (TNFalpha) or interleukin (IL)-1beta but not with IL-4 or interferon gamma (IFNgamma) alone [13].
• We here report the identification of a novel human endothelial cell-specific molecule (called ESM-1) cloned from a human umbilical vein endothelial cell (HUVEC) cDNA library [13].
• In the present study, we have cloned and sequenced 3,888 bp of the 5' flanking region of the human ESM-1 gene [14].
• In vitro, ESM-1 interferes with the molecular mechanisms of immune cell migration by binding to adhesion molecules [6].

Anatomical context of ESM1

• A cell-free system using a Biacore biosensor confirmed that ESM-1 and LFA-1 dynamically interacted in real time with high affinity (K(d) = 18.7 nM) [12].
• Here, we demonstrate that ESM-1 binds directly to LFA-1 onto the cell surface of human blood lymphocytes, monocytes, and Jurkat cells [12].
• A rabbit immune serum raised against the 14-kDa COOH-terminal peptide of ESM-1 immunoprecipitated a 20-kDa protein only in ESM-1-transfected COS cells [13].
• Constitutive ESM-1 gene expression (as demonstrated by Northern blot and reverse transcription-polymerase chain reaction analysis) was found in HUVECs but not in the other human cell lines tested [13].
• ESM-1 expression in human adipocytes was stimulated by phorbol ester, an activator of protein kinase C, and by retinoic acid, an activator of nuclear receptors [6].

Associations of ESM1 with chemical compounds

• Direct binding of ESM-1 to LFA-1 integrin was demonstrated by specific coimmunoprecipitation by CD11a and CD18 mAbs [12].
• The binding of ESM-1 was equally dependent on Ca(2+), Mg(2+), or Mn(2+) divalent ions, which are specific, saturable, and sensitive to temperature [12].
• Cortisol inhibited ESM-1 gene expression in preadipocytes [9].

Other interactions of ESM1

• Identification of endothelial cell genes expressed in an in vitro model of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM [15].
• Analysis of the identified sequences revealed an upregulation of several mRNAs with adenine and uracil-rich elements (ARE) in their 3'-untranslated regions, such as IL-8, ESM-1 and VCAM-1 [16].

Analytical, diagnostic and therapeutic context of ESM1

• Southern blot analysis suggests that a single gene encodes ESM-1 [13].
• Endocan / ESM-1 is a biomarker in sepsis [17]
• Mouse anti-ESM-1 monoclonal antibodies were developed, and three distinct epitopes were mapped, which allowed development of a specific ELISA assay, immunohistological staining and immunoblot analysis [7].
• By microarray, it was shown that Endocan / ESM-1 is a biomarker of tip cells [18]
• Immunoblotting and immunoprecipitation of HUVEC lysates revealed a specific 20-kDa band corresponding to endocan also called ESM-1 [13]
• Gene expression was quantified by TaqMan RT-PCR using specific human and rat ESM-1 primers [6].
• The cellular localisation of ESM-1 was determined by confocal microscopy using a specific antibody [6].

References