ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier

Drolez, Aurore; Vandenhaute, Elodie; Delannoy, Clément Philippe; Dewald, Justine H.; Gosselet, Fabien; Cecchelli, Roméo; Julien, Sylvain; Dehouck, Marie‐Pierre; Delannoy, Philippe; Mysiorek, Caroline

doi:10.3390/ijms17081309

Cited by 45 publications

(32 citation statements)

References 24 publications

(44 reference statements)

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“…ST6GALNAC5, a direct target of miR-200c, is a specific mediator of BCBM [67]. Conversely, the upregulation of ST6GALNAC5 in brain-tropic BC cells showed a decrease in adhesive properties of the endothelial component of a well-characterized human BBB in vitro model [113]. ST6GALNAC5 can also regulate the EMT process in BM and is a target of miR-200b [68].…”

Section: Extravasationmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.Keywords: Breast cancer brain metastasis, miRNA, Brain tumor microenvironment, Blood-brain barrier, CNS metastasis

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Section: Extravasationmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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“…Another published method is the use of umbilical cord blood-derived hematopoietic stem cells for differentiation into endothelial cells, followed by the induction of BBB properties by co-culture with brain pericytes [12][13][14]. These advances in in vitro BBB modelling contribute to advances in the understanding of CNS disorders, such as brain metastases of breast cancer [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood–brain barrier model

Curtaz

Schmitt

Herbert

et al. 2020

Fluids Barriers CNS

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Background: The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB). Methods: We adapted and validated the CD34 + cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. Results: The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment. Conclusion: We demonstrate that the CD34 + cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with

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“…Moreover, ST6GALNAC5 was shown to improve the capacity of breast cancer cells to transmigrate across an in vitro model of the blood–brain barrier (BBB) based on human umbilical vein endothelial cells (HUVECs) . However, with a CD34 + ‐derived human BBB model it was recently shown that ST6GALNAC5 cDNA expression resulted in decreased interactions between MDA‐MB‐231 breast cancer cells and the CD34 + ‐derived human BBB model …”

Section: Expression and Functions In Cancersmentioning

confidence: 99%

Gangliosides: Structures, Biosynthesis, Analysis, and Roles in Cancer

2017

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Gangliosides are acidic glycosphingolipids containing one or more sialic acid residues. They are essential compounds at the outer leaflet of the plasma membrane, where they interact with phospholipids, cholesterol, and transmembrane proteins, forming lipid rafts. They are involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly governed by the glycan moiety, and changes in the structures of gangliosides occur under pathological conditions, particularly in neuro‐ectoderm‐derived cancers. With the progress in mass spectrometry analysis of gangliosides, their role in cancer progression can be now investigated in more detail. In this review we summarize the current knowledge on the biosynthesis of gangliosides and their role in cancers, together with the recent development of cancer immunotherapy targeting gangliosides.

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ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier

Cited by 45 publications

References 24 publications

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood–brain barrier model

Gangliosides: Structures, Biosynthesis, Analysis, and Roles in Cancer

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