Two E-selectin ligands, BST-2 and LGALS3BP, predict metastasis and poor survival of ER-negative breast cancer

Int J Oncol. 2016 Jul;49(1):265-75. doi: 10.3892/ijo.2016.3521. Epub 2016 May 13.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Disease-Free Survival
  • E-Selectin / biosynthesis*
  • E-Selectin / genetics
  • Estrogen Receptor alpha / genetics
  • Female
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Humans
  • Lewis X Antigen / genetics
  • Ligands
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Sialyl Lewis X Antigen

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • BST2 protein, human
  • Biomarkers, Tumor
  • Carrier Proteins
  • E-Selectin
  • Estrogen Receptor alpha
  • GPI-Linked Proteins
  • Glycoproteins
  • LGALS3BP protein, human
  • Lewis X Antigen
  • Ligands
  • Sialyl Lewis X Antigen