ArticleBMC cancer2014
Human breast cancer and lymph node metastases express Gb3 and can be targeted by STxB-vectorized chemotherapeutic compounds.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 43 citations in OpenAlex.
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- The Gb3-synthase A4GALT is an epigenetically regulated driver of tumor invasiveness in gastrointestinal cancer.BMC cancer · 2026Article
- A novel SadP-scFv UCHT1 lectibody activates T cells and mediates lysis of Burkitt's lymphoma cells.RSC chemical biology · 2026Article
- Human Gb3/CD77 synthase: a glycosyltransferase at the crossroads of immunohematology, toxicology, and cancer research.Cellular & molecular biology letters · 2024Review
- Emerging role of MAPK signaling in glycosphingolipid-associated tumorigenesis.Glycoconjugate journal · 2024Review
- New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.Cell communication and signaling : CCS · 2024Review
- Dimeric Lectin Chimeras as Novel Candidates for Gb3-Mediated Transcytotic Drug Delivery through Cellular Barriers.Pharmaceutics · 2023Article
- Novel lectin-based chimeric antigen receptors target Gb3-positive tumour cells.Cellular and molecular life sciences : CMLS · 2022Article
- Sphingolipids and Lymphomas: A Double-Edged Sword.Cancers · 2022Review
- Signaling domains of cancer-associated glycolipids.Glycoconjugate journal · 2022Review
- Shiga Toxin-B Targeted Gold Nanorods for Local Photothermal Treatment in Oral Cancer Clinical Samples.International journal of nanomedicine · 2022Article
- Role of Globotriaosylceramide in Physiology and Pathology.Frontiers in molecular biosciences · 2022Review
- Targeting Nanomaterials to Head and Neck Cancer Cells Using a Fragment of the Shiga Toxin as a Potent Natural Ligand.Cancers · 2021Article
- Shiga Toxins as Antitumor Tools.Toxins · 2021Review
- The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery-The GL-Lect Hypothesis.Molecules (Basel, Switzerland) · 2021Review
- Therapeutic Uses of Bacterial Subunit Toxins.Toxins · 2021Review
- Review
- Deciphering the Importance of Glycosphingolipids on Cellular and Molecular Mechanisms Associated with Epithelial-to-Mesenchymal Transition in Cancer.Biomolecules · 2021Review
- Shiga-Like Toxin Produced by Local Isolates ofBreast cancer : basic and clinical research · 2021Article
- Structural Diversities of Lectins Binding to the Glycosphingolipid Gb3.Frontiers in molecular biosciences · 2021Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe B-subunit of Shiga toxin (STxB) specifically binds to the glycosphingolipid Gb3 that is highly expressed on a number of human tumors and has been shown to target tumor cells in mouse models and ex vivo on primary colon carcinoma specimen.
methodsUsing a novel ex vivo STxB labeling (ESL) method we studied Gb3 expression in cytological specimens of primary human breast tumors from 107 patients, and in synchronous lymph node metastases from 20 patients. Fluorescent STxB was incubated with fine-needle aspiration (FNA) specimens, and Gb3 expression was evaluated by fluorescence microscopy. Furthermore, 11 patient-derived human breast cancer xenografts (HBCx) were evaluated for expression of Gb3 by ESL and FACS. In addition, the biodistribution of fluorescent STxB conjugate was studied after intravenous injection in a Gb3 positive HBCx model.
resultsGb3 expression was detected in 62 of 107 patients (57.9%), mainly in epithelial tumor cells. Gb3 positivity correlated with estrogen receptor expression (p≤0.01), whereas absence of Gb3 expression in primary tumors was correlated with the presence of lymph node metastases (p≤0.03). 65% of lymph node metastases were Gb3 positive and in 40% of tested patients, we observed a statistically significant increase of metastatic Gb3 expression (p≤0.04). Using concordant ESL and flow cytometry analysis, 6 out of 11 HBCx samples were scored positive. Intravenous injections of fluorescent STxB into HBC xenografted mice showed preferential STxB accumulation in epithelial cells and cells with endothelial morphology of the tumor.
conclusionThe enhanced expression of Gb3 in primary breast carcinomas and its lymph node metastases indicate that the development of STxB-based therapeutic strategies is of interest in this pathology. Gb3 expressing HBCx can be used as a model for preclinical studies with STxB conjugates. Finally, the ESL technique on FNA represents a rapid and cost effective method for the stratification of patients in future clinical trials.
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