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Highlight on Mouse Endocan

2015; Lippincott Williams & Wilkins; Volume: 116; Issue: 8 Linguagem: Inglês

10.1161/circresaha.115.306353

1524-4571

Nathalie De Freitas Caires, Philippe Lassalle,

Pancreatitis Pathology and Treatment

HomeCirculation ResearchVol. 116, No. 8Highlight on Mouse Endocan Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBHighlight on Mouse Endocan Nathalie De Freitas Caires Philippe Lassalle Nathalie De Freitas CairesNathalie De Freitas Caires Lunginnov, Lille, France Philippe LassallePhilippe Lassalle Institut National de la Santé et de la Recherche Médicale, U1019, Institut Pasteur de Lille, Lille, France Originally published10 Apr 2015https://doi.org/10.1161/CIRCRESAHA.115.306353Circulation Research. 2015;116:e69–e70To the Editor:There are now emerging data involving the endothelial cell–derived human endocan as a key actor of the tumor progression. Little, however, is known about mouse endocan, until recently. Two novel reports, 1 from Circulation Research1 describing the effects of the genetic deletion of endocan on angiogenesis and inflammation and the other from Oncotarget2 describing specific biochemical and functional characters for mouse endocan lift the veil on how can mouse endocan act, unexpectedly not so similar to its human counterpart.What Is Human Endocan?Human endocan is a product of a unique gene called esm1. It circulates as a dermatan sulfate proteoglycan constituted of a mature polypeptide of 165 aminoacids and a dermatan sulfate chain of 15 to 30 kDa O-glycanated on the serine 137.3 Endocan is overexpressed by specialized endothelial tip cells.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 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. It promotes vascular sprouting and vascular endothelial growth factor–induced migration of endothelial cells.4,7 In addition, endocan shows a potential anti-inflammatory activity through inhibition of the LFA-1 (leukocyte function antigen)–dependent leukocyte function, which could contribute to its net protumoral activity.8What Is Mouse Endocan?The mouse endocan gene has been cloned first in our laboratory in 1999 (Genbank accession number AJ249354). It encodes for a mature polypeptide of 165 aminoacids with 72% homology and conserved structural domains.9 Mouse endocan also circulates freely at ≈1 ng/mL.9 Consistently, mouse endocan was found expressed in endothelial tip cells from several retinal angiogenesis models.10 The Aird's group demonstrated overexpression of mouse endocan by tumor endothelial cells in xenogenic tumors,11 but they also found that mouse endocan is spontaneously produced by nonendothelial cells from lung, kidney, and spleen.11Using endocan knockout mice, Rocha et al1 reported recently in Circulation Research that endocan is required for optimal response to vascular endothelial growth factor (less endothelial filopodia and less cerebral edema in knockout mice). Interestingly, endocan was shown to increase the recruitment of leukocytes 2 to 4 hours after intraperitoneal injection of interleukin-1β. More recently, Yassine et al2 reported in Oncotarget that mouse endocan is much less glycanated than its human counterpart. Surprisingly, the non–glycanated endocan seems to favor the recruitment of leukocytes into the experimental solid tumors.Both Rocha's and Yassine's reports support the idea that the main circulating form of endocan in healthy mice is nonendothelial and nonglycanated, different from the main human circulating form, which is endothelial-derived and full glycanated. Each of these forms has potential opposite biological properties depending on its glycanic status: protumoral and anti-inflammatory for the glycanated form; antitumoral and proinflammatory for the non-glycanated form.Mouse endocan sounds more complex than its human counterpart. Several unanswered questions remain. Quid on the glycan status and the function(s) of the true endothelial cell–derived endocan overexpressed by vessels from experimental tumors? Which common pathways endocan uses in the so different clinical contexts like inflammation or cancer? A fascinating exploratory domain is now open which could conduct to the control of tumor progression by regulating inflammation.Nathalie De Freitas CairesLunginnovLille, FrancePhilippe LassalleInstitut National de la Santé et de la Recherche Médicale,U1019Institut Pasteur de LilleLille, FranceDisclosuresNone.FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment.References1. Rocha SF, Schiller M, Jing D, Li H, Butz S, Vestweber D, Biljes D, Drexler HC, Nieminen-Kelhä M, Vajkoczy P, Adams S, Benedito R, Adams RH.Esm1 modulates endothelial tip cell behavior and vascular permeability by enhancing VEGF bioavailability.Circ Res. 2014; 115:581–590. doi: 10.1161/CIRCRESAHA.115.304718.LinkGoogle Scholar2. Yassine H, De Freitas Caires N, Depontieu F, Scherpereel A, Awad A, Tsicopoulos A, Leboeuf C, Janin A, Duez C, Grigoriu B, Lassalle P.The non glycanated endocan polypeptide slows tumor growth by inducing stromal inflammatory reaction.Oncotarget. 2015; 6:2725–2735.CrossrefMedlineGoogle Scholar3. Sarrazin S, Lyon M, Deakin JA, Guerrini M, Lassalle P, Delehedde M, Lortat-Jacob H.Characterization and binding activity of the chondroitin/dermatan sulfate chain from Endocan, a soluble endothelial proteoglycan.Glycobiology. 2010; 20:1380–1388. doi: 10.1093/glycob/cwq100.CrossrefMedlineGoogle Scholar4. Roudnicky F, Poyet C, Wild P, Krampitz S, Negrini F, Huggenberger R, Rogler A, Stöhr R, Hartmann A, Provenzano M, Otto VI, Detmar M.Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis.Cancer Res. 2013; 73:1097–1106. doi: 10.1158/0008-5472.CAN-12-1855.CrossrefMedlineGoogle Scholar5. Delehedde M, Devenyns L, Maurage CA, Vivès RR.Endocan in cancers: a lesson from a circulating dermatan sulfate proteoglycan.Int J Cell Biol. 2013; 2013:705027. doi: 10.1155/2013/705027.CrossrefMedlineGoogle Scholar6. Scherpereel A, Gentina T, Grigoriu B, Sénéchal S, Janin A, Tsicopoulos A, Plénat F, Béchard D, Tonnel AB, Lassalle P.Overexpression of endocan induces tumor formation.Cancer Res. 2003; 63:6084–6089.MedlineGoogle Scholar7. Shin JW, Huggenberger R, Detmar M.Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis.Blood. 2008; 112:2318–2326. doi: 10.1182/blood-2008-05-156331.CrossrefMedlineGoogle Scholar8. Béchard D, Scherpereel A, Hammad H, Gentina T, Tsicopoulos A, Aumercier M, Pestel J, Dessaint JP, Tonnel AB, Lassalle P.Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1.J Immunol. 2001; 167:3099–3106.CrossrefMedlineGoogle Scholar9. Depontieu F, de Freitas Caires N, Gourcerol D, Giordano J, Grigoriu B, Delehedde M, Lassalle P.Development of monoclonal antibodies and ELISA specific for the mouse vascular endocan.J Immunol Methods. 2012; 378:88–94. doi: 10.1016/j.jim.2012.02.009.CrossrefMedlineGoogle Scholar10. del Toro R, Prahst C, Mathivet T, Siegfried G, Kaminker JS, Larrivee B, Breant C, Duarte A, Takakura N, Fukamizu A, Penninger J, Eichmann A.Identification and functional analysis of endothelial tip cell-enriched genes.Blood. 2010; 116:4025–4033. doi: 10.1182/blood-2010-02-270819.CrossrefMedlineGoogle Scholar11. Abid MR, Yi X, Yano K, Shih SC, Aird WC.Vascular endocan is preferentially expressed in tumor endothelium.Microvasc Res. 2006; 72:136–145. doi: 10.1016/j.mvr.2006.05.010.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gaudet A, Portier L, Prin M, Copin M, Tsicopoulos A, Mathieu D, Lassalle P and De Freitas Caires N (2019) Endocan regulates acute lung inflammation through control of leukocyte diapedesis, Journal of Applied Physiology, 10.1152/japplphysiol.00337.2019, 127:3, (668-678), Online publication date: 1-Sep-2019. Sagara A, Igarashi K, Otsuka M, Kodama A, Yamashita M, Sugiura R, Karasawa T, Arakawa K, Narita M, Kuzumaki N, Narita M and Kato Y (2016) Endocan as a prognostic biomarker of triple-negative breast cancer, Breast Cancer Research and Treatment, 10.1007/s10549-016-4057-8, 161:2, (269-278), Online publication date: 1-Jan-2017. April 10, 2015Vol 116, Issue 8 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.115.306353PMID: 25858072 Originally publishedApril 10, 2015 PDF download Advertisement SubjectsVascular Biology