title: Two E-selectin ligands, BST-2 and LGALS3BP, predict metastasis and poor survival of ER-negative breast cancer.
abstract: Distant metastases account for the majority of cancer-related deaths in breast cancer. The rate and site of metastasis differ between estrogen receptor (ER)-negative and ER-positive tumours, and metastatic fate can be very diverse even within the ER-negative group. Characterisation of new pro-metastatic markers may help to identify patients with higher risk and improve their care accordingly. Selectin ligands aberrantly expressed by cancer cells promote metastasis by enabling interaction between circulating tumour cells and endothelial cells in distant organs. These ligands consist in carbohydrate molecules, such as sialyl-Lewis x antigen (sLex), borne by glycoproteins or glycolipids on the cancer cell surface. We have previously demonstrated that the molecular scaffold presenting sLex to selectins (e.g. glycolipid vs. glycoproteins) was crucial for these interactions to occur. Moreover, we reported that detection of sLex alone in breast carcinomas was only of limited prognostic value. However, since sLex was found to be carried by several glycoproteins in cancer cells, we hypothesized that the combination of the carbohydrate with its carriers could be more relevant than each marker independently. In this study, we addressed this question by analysing sLex expression together with two glycoproteins (BST-2 and LGALS3BP), shown to interact with E-selectin in a carbohydrate-dependent manner, in a cohort of 249 invasive breast cancers. We found both glycoproteins to be associated with distant metastasis risk and poorer survival. Importantly, concomitant high expression of BST-2 with sLex defined a sub-group of patients with ER-negative tumours displaying higher risks of liver and brain metastasis and a 3-fold decreased survival rate.
authors.affiliation: Breast Research Pathology, King's College London, Guy's Hospital, London, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Woodman
authors.affiliation: Breast Research Pathology, King's College London, Guy's Hospital, London, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: Breast Cancer Biology, Research Oncology, King's College London, Guy's Hospital, London, UK.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tajadura
authors.affiliation: University of Lille, INSERM, U908 - CPAC, Cell Plasticity and Cancer, Lille, Villeneuve d'Ascq, France.
authors.forename: Xuefen
authors.initials: X
authors.lastname: Le Bourhis
authors.affiliation: Breast Research Pathology, King's College London, Guy's Hospital, London, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gillett
authors.affiliation: University of Lille, CNRS, UMR 8576 - UGSF, Unit of Structural and Functional Glycobiology, Lille, Villeneuve d'Ascq, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
authors.affiliation: Breast Cancer Biology, Research Oncology, King's College London, Guy's Hospital, London, UK.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Burchell
authors.affiliation: University of Lille, INSERM, U908 - CPAC, Cell Plasticity and Cancer, Lille, Villeneuve d'Ascq, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Julien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016256:Lewis X Antigen / Q000235:genetics; D008024:Ligands; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D000080506:Sialyl Lewis X Antigen; D000074010:Bone Marrow Stromal Antigen 2; D016326:Extracellular Matrix Proteins
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D019040:E-Selectin; D047628:Estrogen Receptor alpha; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D016256:Lewis X Antigen; D008024:Ligands; D000080506:Sialyl Lewis X Antigen; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins