title: Carcinoma-associated fucosylated antigens are markers of the epithelial state and can contribute to cell adhesion through CLEC17A (Prolectin).
abstract: Terminal fucosylated motifs of glycoproteins and glycolipid chains are often altered in cancer cells. We investigated the link between fucosylation changes and critical steps in cancer progression: epithelial-to-mesenchymal transition (EMT) and lymph node metastasis.Using mammary cell lines, we demonstrate that during EMT, expression of some fucosylated antigens (e.g.: Lewis Y) is decreased as a result of repression of the fucosyltransferase genes FUT1 and FUT3. Moreover, we identify the fucose-binding bacterial lectin BC2L-C-Nt as a specific probe for the epithelial state.Prolectin (CLEC17A), a human lectin found on lymph node B cells, shares ligand specificities with BC2L-C-Nt. It binds preferentially to epithelial rather than to mesenchymal cells, and microfluidic experiments showed that prolectin behaves as a cell adhesion molecule for epithelial cells. Comparison of paired primary tumors/lymph node metastases revealed an increase of prolectin staining in metastasis and high FUT1 and FUT3 mRNA expression was associated with poor prognosis. Our data suggest that tumor cells invading the lymph nodes and expressing fucosylated motifs associated with the epithelial state could use prolectin as a colonization factor.
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.|Nantes University Hospital, 44007 Nantes, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Breiman
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: López Robles
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: de Carné Trécesson
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.|Recombinant Protein Core Facility of The University of Nantes, 44007 Nantes, France.
authors.forename: Klara
authors.initials: K
authors.lastname: Echasserieau
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.|Recombinant Protein Core Facility of The University of Nantes, 44007 Nantes, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Bernardeau
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7, UK.
authors.forename: Kurt
authors.initials: K
authors.lastname: Drickamer
authors.affiliation: CERMAV-UPR 5301, CNRS, Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Barillé-Nion
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Altare
authors.affiliation: Inserm U892, CNRS UMR6299, University of Nantes, 44007 Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Pendu
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D014407:Tumor Cells, Cultured; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D014408:Biomarkers, Tumor; D005647:Fucosyltransferases; D037181:Lectins, C-Type; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C578707:CLEC17A protein, human; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
keywords: epithelial to mesenchymal transition; fucose; lectins; lymph node metastasis