{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:13:52Z","timestamp":1787015632605,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>GD2, a member of the ganglioside (GS) family (sialic acid\u2010containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The stem\u2010like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT\u2010qPCR. The modulation of stem features by GS was investigated in\u00a0vitro and in\u00a0vivo using GD3S\u2010overexpressing cells and corroborated by global transcriptomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GS composition was markedly different comparing SPH and MON. Among complex GS, iCCA\u2010SPH showed increased GD2 levels, in agreement with the high expression levels of GD3 and GM2\/GD2 synthases. iCCA cells overexpressing GD3S had higher sphere\u2010forming ability, invasive properties and drug resistance than parental cells. NOD\/SCID mice implanted with CCLP1 cells overexpressing GD3S developed larger tumours than control cells. By global transcriptomic analysis, ontology investigation identified 74 processes shared by the iCCA\u2010SPH and GD3S\u2010transfected cells, with enrichment for development and morphogenesis processes, MAPK signalling and locomotion. In a cohort of patients with iCCA, GD3S expression was correlated with lymph node invasion, indicating a possible relevance of GD3S in the clinical setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The profile of GS derivatives regulates the stem\u2010like properties of iCCA cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.16208","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T01:35:10Z","timestamp":1735263310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ganglioside\n                    <scp>GD2<\/scp>\n                    Contributes to a Stem\u2010Like Phenotype in Intrahepatic Cholangiocarcinoma"],"prefix":"10.1111","volume":"45","author":[{"given":"Antonella","family":"Mannini","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Pastore","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Giachi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Correnti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sp\u00ednola Lasso","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziano","family":"Lottini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Piombanti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazia","family":"Tusa","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u2018Mario Serio\u2019 University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Rovida","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u2018Mario Serio\u2019 University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Coulouarn","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, Inra Institut NUMECAN (Nutrition Metabolisms and Cancer)\u2010UMR_S 1241, UMR_A 1341  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-5244","authenticated-orcid":false,"given":"Jesper B.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Centre University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Lewinska","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Centre University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Campani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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