Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Julien, Sylvain; Ivetic, Aleksandar; Grigoriadis, Anita; QiZe, Ding; Burford, Brian; Sproviero, Daisy; Picco, Gianfranco; Gillett, Cheryl; Papp, Suzanne L.; Schaffer, Lana; Tutt, Andrew; Taylor‐Papadimitriou, Joyce; Pinder, Sarah; Burchell, Joy

doi:10.1158/0008-5472.can-11-1139

Cited by 163 publications

(149 citation statements)

References 45 publications

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“…We first analysed the association of each of the three markers with several histological and clinical features of the tumours (Table II). As previously reported (12), sLe x high expression correlated with ER-negativity, lymph node (LN) involvement, and high grade. We also observed a correlation with progesterone receptor (PR) negativity.…”

Section: Resultssupporting

confidence: 74%

“…Although ER-negative cancers are known to typically be of higher grade and intrinsically more aggressive and more often develop metastatic foci, we found no evidence that sLe x was correlated with metastatic behaviour either in the ER-negative or the ER-positive group (7).…”

Section: Introductioncontrasting

confidence: 88%

“…1). This panel included the ZR-75-1 for which both BST-2 and LGALS3BP staining were positive, according to the fact that these proteins were immuno-precipitated from this particular cell line (7). The staining of biopsies was independently scored by two observers (S.J.…”

Section: Tissue Microarray (Tma) Construction and Analysismentioning

confidence: 99%

“…There is a compelling body of evidence that sLe x /selectin interaction is involved in metastatic progression in several types of solid tumours including gastric (4), lung (5) and prostate (6) cancers. However, the relationship in breast cancer metastasis remains controversial (7).…”

Section: Introductionmentioning

confidence: 99%

“…We identified two of these glycoproteins as tetherin, also known as bone marrow stromal antigen 2 (BST-2), and the galectin-3-binding protein (also named MAC-2BP) encoded by the LGALS3BP gene (7). Subsequently, Shirure et al have shown that MAC-2BP carrying sLe x was functionally involved in ZR-75-1 rolling on HUVECs cultured as monolayer (8).…”

Section: Introductionmentioning

confidence: 99%

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

Woodman¹,

Pinder²,

Tajadura³

et al. 2016

International Journal of Oncology

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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 (sLe x ), borne by glycoproteins or glycolipids on the cancer cell surface. We have previously demonstrated that the molecular scaffold presenting sLe x to selectins (e.g. glycolipid vs. glycoproteins) was crucial for these interactions to occur. Moreover, we reported that detection of sLe x alone in breast carcinomas was only of limited prognostic value. However, since sLe x 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 sLe x 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 sLe x defined a subgroup of patients with ER-negative tumours displaying higher risks of liver and brain metastasis and a 3-fold decreased survival rate.

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Section: Resultssupporting

confidence: 74%

Section: Introductioncontrasting

confidence: 88%

Section: Tissue Microarray (Tma) Construction and Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Woodman¹,

Pinder²,

Tajadura³

et al. 2016

International Journal of Oncology

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The sialyltransferase ST3Gal3 facilitates the receptivity of the uterine endometrium in vitro and in vivo

Wang

Liu

et al. 2018

FEBS Letters

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The receptive uterine endometrium specifically expresses certain glycosyltransferases, and the corresponding oligosaccharides play important roles in accepting the embryo. The sialyltransferase β-galactoside-α2,3-sialyltransferase III (ST3Gal3) is the key enzyme responsible for sialyl Lewis X (sLeX) oligosaccharide biosynthesis, but the expression and function of ST3Gal3 in the receptive endometrium is still elusive. Here, we found that human endometrial tissues at secretory phase expressed a 4-fold higher ST3Gal3 level relative to the tissues at proliferative phase. Meanwhile, downregulation of ST3Gal3 or sLeX epitope blockage significantly impaired the receptive ability of human endometrial RL95-2 cells to trophoblastic cells in vitro and inhibited implantation in pregnant mice. This study suggests that ST3Gal3 facilitates endometrial receptivity through increasing sLeX oligosaccharide, which gives a better understanding of the glycobiology of implantation.

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Inhibition of fucosylation in human invasive ductal carcinoma reduces E‐selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation

et al. 2018

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Breast cancer tissue overexpresses fucosylated glycans, such as sialyl‐Lewis X/A (sLeX /A), and α‐1,3/4‐fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E‐selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLeX /A, to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E‐selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E‐selectin and anti‐sLeX /A antibodies in both IDC tissue and cell lines, and expression of α‐1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the ‘CF1_T cell line’. Treatment with 2‐fluorofucose (2‐FF), a fucosylation inhibitor, completely abrogated its sLeX /A expression and dramatically reduced adherence of CF1_T cells to E‐selectin under hemodynamic flow conditions. In addition, 2‐FF‐treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2‐FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal‐regulating protein kinases 1 and 2 and p38 mitogen‐activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.

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Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Cited by 163 publications

References 45 publications

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

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

The sialyltransferase ST3Gal3 facilitates the receptivity of the uterine endometrium in vitro and in vivo

Inhibition of fucosylation in human invasive ductal carcinoma reduces E‐selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation

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