Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer

Stübke, Katrin; Wicklein, Daniel; Herich, Lena; Schumacher, Udo; Nehmann, Nina

doi:10.1016/j.canlet.2012.02.019

Cited by 45 publications

(50 citation statements)

References 51 publications

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“…Based on new biomarkers, such as our BST-2/sLe x combination, one may therefore consider improving ER-negative patients follow-up and treatment protocols with possibly more aggressive therapy. On the other hand, such biomarkers, presumably involved in selectinmediated metastasis (28), could also serve as molecular target for tailored therapy (29). In that regard, we believe both BST-2 and LGALS3BP could be considered as putative targets to treat ER-negative metastatic breast cancer.…”

Section: Discussionmentioning

confidence: 98%

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: Discussionmentioning

confidence: 98%

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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“…Lactosaminyl glycan-based epitopes and their selectin receptors are also important for the homing of stem cells to bone marrow niches (31,32), and recent indications suggest that differential glycan recognition may serve as a checkpoint between hematopoietic stem cell (HSC) quiescence and proliferation (33). Selectin and lactosaminyl glycan epitopes have also been implicated in breast cancer stem cell dissemination and metastatic lodgment (34,35). Just how these critical cell surface glycans are regulated biosynthetically remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Remodeling of Marrow Hematopoietic Stem and Progenitor Cells by Non-self ST6Gal-1 Sialyltransferase

Nasirikenari

Veillon

Collins

et al. 2014

Journal of Biological Chemistry

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Background: The circulatory ST6Gal-1 level is inversely related to hematopoietic activity, but the biochemical function of systemic ST6Gal-1 is unknown. Results: Hematopoietic progenitors do not express self-ST6Gal-1 but are acted upon by remotely produced enzyme. Conclusion: Distally produced rather than endogenous ST6Gal-1 is the principal modifier of the early hematopoietic progenitor cell surface. Significance: Extrinsic ST6Gal-1 may be a potent systemic regulator of hematopoiesis.

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“…À/À mice (13)(14)(15). Likewise, engraftment and organ invasion of human eosinophilic leukemia cells (EOL-1) are remarkably reduced in selectin-deficient mice (16).…”

Section: /Rag2mentioning

confidence: 99%

“…For VCaP tumor growth, it was necessary to mix 1 Â 10 6 cells 1:2 with Matrigel (BD Biosciences) immediately before injection. Pfp/Rag2 À/À mice were crossbred with E-and P-selectin-deficient mice (Jackson Laboratory, stock 002916) and selectin deficiency was verified as described (13).…”

Section: Ht29mentioning

confidence: 99%

“…1A, these glycans are common intermediates for the synthesis of sialylated Lewis X and A antigens (sLe X and sLe A ; ref. 12), which are presented at the surface of human breast and gastrointestinal adenocarcinoma (13)(14)(15) as well as leukemia cells (16). sLeX and sLeA are the main ligands for E-and P-selectin and therefore crucially involved in the adhesion cascade of leukocytes into inflamed tissues (17).…”

Section: Introductionmentioning

confidence: 99%

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Aberrant Presentation of HPA-Reactive Carbohydrates Implies Selectin-Independent Metastasis Formation in Human Prostate Cancer

Lange

Kupfernagel

Wicklein

et al. 2014

Clinical Cancer Research

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Purpose: To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cellendothelial cell interaction in prostate cancer metastasis.Experimental Design: Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epithelium. Prostate cancer cells were examined for HPA-and selectinbinding and adhesion to endothelium. Spontaneous metastasis xenograft models were established to test the lectin HPA-binding sites as a marker of metastatic competence and to evaluate E-selectin-binding sites in vivo. The importance of selectins for metastasis formation was analyzed using Seleclinical relevance of HPA-and E-selectin-binding sites in prostate cancer was determined.Results: Glycosyltransferases involved in the synthesis of common HPA-binding sites are downregulated in prostate cancer cells. An absence of HPA-reactive carbohydrates specifically indicates spontaneous metastatic spread of prostate cancer xenografts in vivo and a poor prognosis of patients with prostate cancer. HPA-binding sites decrease in lymph node metastases compared with corresponding primary tumors. Common selectin ligands are absent on prostate cancer cells, which do not adhere to recombinant selectins or endothelium under shear stress in vitro. Spontaneous metastasis formation is largely independent of selectins in vivo. E-selectin-binding sites are detectable in only 2% of patients with prostate cancer without prognostic significance.Conclusion: Prostate cancer is characterized by an inverse functional and prognostic importance of HPAbinding sites compared with other adenocarcinomas. Accordingly, this study surprisingly shows that the selectin-selectin ligand axis, which is essential for extravasation and thus metastasis formation in several malignancies, can be circumvented in prostate cancer.

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Selectin-deficiency reduces the number of spontaneous metastases in a xenograft model of human breast cancer

Cited by 45 publications

References 51 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

Remodeling of Marrow Hematopoietic Stem and Progenitor Cells by Non-self ST6Gal-1 Sialyltransferase

Aberrant Presentation of HPA-Reactive Carbohydrates Implies Selectin-Independent Metastasis Formation in Human Prostate Cancer

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