title: The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL.
abstract: Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr) and STn (NeuAcα2,6GalNAc-Ser/Thr). These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell and in close proximity to extended glycan T (Galβ1,3GalNAc) the addition of Gal to the GalNAc being catalysed by the T synthase. The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn can bind to the C-type lectin MGL and using atomic force microscopy show that they bind to MGL with a similar dead adhesion force. Tumour associated STn is associated with poor prognosis and resistance to chemotherapy in breast carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK activity. As engagement of MGL in the absence of TLR triggering may lead to anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the characteristics of STn expressing tumours.
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Beatson
authors.affiliation: Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
authors.forename: Gjertrud
authors.initials: G
authors.lastname: Maurstad
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Picco
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Appitha
authors.initials: A
authors.lastname: Arulappu
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Coleman
authors.affiliation: Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandell
authors.affiliation: Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.affiliation: Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Joyce
authors.initials: J
authors.lastname: Taylor-Papadimitriou
authors.affiliation: Department of Physics, Norwegian University of Science and Technology, 7491, Trondheim, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Sletmoen
authors.affiliation: Breast Cancer Biology, King's College London, Guy's Hospital, London, SE1 9RT, United Kingdom.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Burchell
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037181:Lectins, C-Type; C506225:MGL lectin, human; C060192:MUC1 protein, human; D018396:Mucin-1; C040286:Tn antigen