title: Carbohydrate-to-carbohydrate interactions between α2,3-linked sialic acids on α2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells.
abstract: Complex interplays among proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the GSLs (glycosphingolipids), AsGM1 (asialo-GM1), which lacks α2,3-linked sialic acid, and α2β1 integrin receptors is responsible for the metastatic behaviour of C4-2B prostate cancer cells. Herein, we identified and addressed the functional significance of changes in sialylation during prostate cancer progression. We observed an increase in α2,3-linked sialic acid residues on α2 subunits of α2β1 integrin receptors, correlating with increased gene expression of α2,3-STs (sialyltransferases), particularly ST3GAL3. Cell surface α2,3-sialylation of α2 subunits was required for the integrin α2β1-dependent cell adhesion to collagen type I and the same α2,3-linked sialic acid residues on the integrin receptor were responsible for the interaction with the carbohydrate moiety of AsGM1, explaining the complex formation between AsGM1 and α2β1 integrin receptors. These results provide novel insights into the role of sialic acids in the organization and function of important membrane components in invasion and metastatic processes.
authors.forename: Séverine
authors.initials: S
authors.lastname: Van Slambrouck
authors.affiliation: †Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS No. 8576, Bâtiment C9, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Groux-Degroote
authors.affiliation: †Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS No. 8576, Bâtiment C9, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, Lille, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Krzewinski-Recchi
authors.affiliation: †Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS No. 8576, Bâtiment C9, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, Lille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazet
authors.affiliation: †Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS No. 8576, Bâtiment C9, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
authors.affiliation: *School of Science, Technology and Engineering Management, St. Thomas University, 16401 NW 37th Avenue, Miami Gardens, FL 33054, USA.
authors.forename: Wim F A
authors.initials: WF
authors.lastname: Steelant
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D005677:G(M1) Ganglioside / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012794:Sialic Acids / Q000235:genetics / Q000378:metabolism*
chemical_list: D039421:Integrin alpha2; D012794:Sialic Acids; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside