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2. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

Author

Anstee, Joanne E., Feehan, Karen T., Opzoomer, James W., Dean, Isaac, Muller, Henrike P., Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E., Lan, Guocheng, Zou, Xiangang, Watt, Fiona M., Ng, Tony, Burchell, Joy M., Kordasti, Shahram, Withers, David R., Lawrence, Toby, and Arnold, James N.

Published
2023
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5. Supplemental Figure 2: Characterization of MUC1-DG75 transfectant cell line and of the MUC1-DG75-MVs. from Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Author

Rughetti, Aurelia, primary, Rahimi, Hassan, primary, Belleudi, Francesca, primary, Napoletano, Chiara, primary, Battisti, Federico, primary, Zizzari, Ilaria G., primary, Antonilli, Morena, primary, Bellati, Filippo, primary, Wandall, Hans H., primary, Benedetti Panici, Pierluigi, primary, Burchell, Joy M., primary, Torrisi, Mara R., primary, and Nuti, Marianna, primary

Published
2023
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6. Supplementary Figure 2 - PDF file - 3056K from Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Author

Rughetti, Aurelia, primary, Rahimi, Hassan, primary, Belleudi, Francesca, primary, Napoletano, Chiara, primary, Battisti, Federico, primary, Zizzari, Ilaria G., primary, Antonilli, Morena, primary, Bellati, Filippo, primary, Wandall, Hans H., primary, Benedetti Panici, Pierluigi, primary, Burchell, Joy M., primary, Torrisi, Mara R., primary, and Nuti, Marianna, primary

Published
2023
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7. Supplemental Figure 1: HLAII-DR molecule accumulates at the periphery of DCs after 12 hours incubation from Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Author

Rughetti, Aurelia, primary, Rahimi, Hassan, primary, Belleudi, Francesca, primary, Napoletano, Chiara, primary, Battisti, Federico, primary, Zizzari, Ilaria G., primary, Antonilli, Morena, primary, Bellati, Filippo, primary, Wandall, Hans H., primary, Benedetti Panici, Pierluigi, primary, Burchell, Joy M., primary, Torrisi, Mara R., primary, and Nuti, Marianna, primary

Published
2023
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8. Supplementary Figure 1 - PDF file - 42K from Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Author

Rughetti, Aurelia, primary, Rahimi, Hassan, primary, Belleudi, Francesca, primary, Napoletano, Chiara, primary, Battisti, Federico, primary, Zizzari, Ilaria G., primary, Antonilli, Morena, primary, Bellati, Filippo, primary, Wandall, Hans H., primary, Benedetti Panici, Pierluigi, primary, Burchell, Joy M., primary, Torrisi, Mara R., primary, and Nuti, Marianna, primary

Published
2023
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9. Data from Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

Author

Rughetti, Aurelia, primary, Rahimi, Hassan, primary, Belleudi, Francesca, primary, Napoletano, Chiara, primary, Battisti, Federico, primary, Zizzari, Ilaria G., primary, Antonilli, Morena, primary, Bellati, Filippo, primary, Wandall, Hans H., primary, Benedetti Panici, Pierluigi, primary, Burchell, Joy M., primary, Torrisi, Mara R., primary, and Nuti, Marianna, primary

Published
2023
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10. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Author

Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, Arnold, James N, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, and Arnold, James N

Abstract

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1 + TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1 + TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8 + T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy.

Published
2023

11. LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Author

Afd Pharmacology, Pharmacology, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, Arnold, James N, Afd Pharmacology, Pharmacology, Anstee, Joanne E, Feehan, Karen T, Opzoomer, James W, Dean, Isaac, Muller, Henrike P, Bahri, Meriem, Cheung, Tik Shing, Liakath-Ali, Kifayathullah, Liu, Ziyan, Choy, Desmond, Caron, Jonathan, Sosnowska, Dominika, Beatson, Richard, Muliaditan, Tamara, An, Zhengwen, Gillett, Cheryl E, Lan, Guocheng, Zou, Xiangang, Watt, Fiona M, Ng, Tony, Burchell, Joy M, Kordasti, Shahram, Withers, David R, Lawrence, Toby, and Arnold, James N

Published
2023

12. Supplementary Figures 1-10, Supplementary Materials and Methods, Supplementary References from Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer

Author

Muliaditan, Tamara, primary, Opzoomer, James W., primary, Caron, Jonathan, primary, Okesola, Mary, primary, Kosti, Paris, primary, Lall, Sharanpreet, primary, Van Hemelrijck, Mieke, primary, Dazzi, Francesco, primary, Tutt, Andrew, primary, Grigoriadis, Anita, primary, Gillett, Cheryl E., primary, Madden, Stephen F., primary, Burchell, Joy M., primary, Kordasti, Shahram, primary, Diebold, Sandra S., primary, Spicer, James F., primary, and Arnold, James N., primary

Published
2023
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13. Supplementary Table from Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer

Author

Muliaditan, Tamara, primary, Opzoomer, James W., primary, Caron, Jonathan, primary, Okesola, Mary, primary, Kosti, Paris, primary, Lall, Sharanpreet, primary, Van Hemelrijck, Mieke, primary, Dazzi, Francesco, primary, Tutt, Andrew, primary, Grigoriadis, Anita, primary, Gillett, Cheryl E., primary, Madden, Stephen F., primary, Burchell, Joy M., primary, Kordasti, Shahram, primary, Diebold, Sandra S., primary, Spicer, James F., primary, and Arnold, James N., primary

Published
2023
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14. Supplementary Movie Legends 1-2 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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15. Supplementary Figure 1 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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16. Supplementary Methods and Results from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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17. Supplementary Tables 1-3 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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18. Supplementary Figure 5 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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19. Supplementary Figure 3 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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20. Data from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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21. Supplementary Figure 2 from Selectin Ligand Sialyl-Lewis x Antigen Drives Metastasis of Hormone-Dependent Breast Cancers

Author

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

Published
2023
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23. Perivascular macrophages collaborate to facilitate chemotherapy resistance in cancer

Author

Anstee, Joanne E., primary, Opzoomer, James W., additional, Dean, Isaac, additional, Muller, Henrike P., additional, Bahri, Meriem, additional, Liakath-Ali, Kifayathullah, additional, Liu, Ziyan, additional, Choy, Desmond, additional, Caron, Jonathan, additional, Sosnowska, Dominika, additional, Beatson, Richard, additional, Muliaditan, Tamara, additional, An, Zhengwen, additional, Gillett, Cheryl E., additional, Lan, Guocheng, additional, Zou, Xiangang, additional, Watt, Fiona M., additional, Ng, Tony, additional, Burchell, Joy M., additional, Kordasti, Shahram, additional, Withers, David R., additional, Lawrence, Toby, additional, and Arnold, James N., additional

Published
2022
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24. LYVE-1 + Macrophages Form a Collaborative CCR5-Dependent Perivascular Niche That Influences Chemotherapy Responses in Cancer

Author

Anstee, Joanne E., primary, Opzoomer, James W., additional, Dean, Isaac, additional, Muller, Henrike P., additional, Bahri, Meriem, additional, Liakath-Ali, Kifayathullah, additional, Liu, Ziyan, additional, Choy, Desmond, additional, Caron, Jonathan, additional, Sosnowska, Dominika, additional, Beatson, Richard, additional, Muliaditan, Tamara, additional, An, Zhengwen, additional, Gillett, Cheryl E., additional, Lan, Guocheng, additional, Zou, Xiangang, additional, Watt, Fiona M., additional, Ng, Tony, additional, Burchell, Joy M., additional, Kordasti, Shahram, additional, Withers, David R., additional, Lawrence, Toby, additional, and Arnold, James N., additional

Published
2022
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27. O-linked mucin-type glycosylation in breast cancer

Author

Burchell, Joy M., Beatson, Richard, Graham, Rosalind, Taylor-Papadimitriou, Joyce, and Tajadura-Ortega, Virginia

Subjects
Acetylgalactosamine, Glycosylation, Glycoside Hydrolases, Golgi Apparatus, Breast Neoplasms, Review Article, Gene Expression Regulation, Enzymologic, breast cancer, Tumor Microenvironment, Humans, Neoplasm Metastasis, skin and connective tissue diseases, Review Articles, Mucin-1, Glycosyltransferases, Biological Transport, Hydrogen-Ion Concentration, lectins, carbohydrates (lipids), Disease Progression, Female, sense organs, immunotherapy, O-linked mucin-type glycosylation
Abstract

Changes in mucin-type O-linked glycosylation are seen in over 90% of breast cancers where increased sialylation is often observed and a change from branched glycans to linear glycans is often seen. There are a number of mechanisms involved including increased/altered expression of glycosyltransferases and relocalization to the endoplasmic reticulum of the enzymes responsible for the addition of the first sugar, N-acetyl-D-galactosamine. It is now becoming clear that these changes can contribute to tumour growth and progression by modulating the microenvironment through glycan sensing lectins expressed on immune cells, by modulating interactions with tumour surface receptors and by binding to selectins. The understanding of how changes in mucin-type O-linked glycosylation influence tumour growth and progression reveals new potential targets for therapeutic intervention in the treatment of breast cancer.

Published
2018
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28. Latest developments in MUC1 immunotherapy

Author

Taylor-Papadimitriou, Joyce, Burchell, Joy M., Graham, Rosalind, and Beatson, Richard

Subjects
Antimetabolites, Antineoplastic, Clinical Trials as Topic, Glycosylation, Mucin-1, MUC1, Review Article, Combined Modality Therapy, Deoxycytidine, Gemcitabine, Neoplasms, Tumor Microenvironment, cancer, Humans, Immunotherapy, Review Articles
Abstract

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. ppbiost;46/3/659/BST20170400CF1F1BST-2017-0400CF1Figure 1.Number of MUC1-targeted trials initiated each year.

Published
2018

34. O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR

Author

Tajadura-Ortega, Virginia, primary, Gambardella, Gennaro, additional, Skinner, Alexandra, additional, Halim, Adnan, additional, Van Coillie, Julie, additional, Schjoldager, Katrine Ter-Borch Gram, additional, Beatson, Richard, additional, Graham, Rosalind, additional, Achkova, Daniela, additional, Taylor-Papadimitriou, Joyce, additional, Ciccarelli, Francesca D, additional, and Burchell, Joy M, additional

Published
2020
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35. Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype

Author

Beatson, Richard, primary, Graham, Rosalind, additional, Freile, Fabio Grundland, additional, Cozzetto, Domenico, additional, Kannambath, Shichina, additional, Pfeifer, Ester, additional, Woodman, Natalie, additional, Owen, Julie, additional, Nuamah, Rosamond, additional, Mandel, Ulla, additional, Pinder, Sarah, additional, Gillett, Cheryl, additional, Noll, Thomas, additional, Bouybayoune, Ihssane, additional, Taylor-Papadimitriou, Joyce, additional, and Burchell, Joy M., additional

Published
2020
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42. O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR in breast cancer

Author

Tajadura-Ortega, Virginia, primary, Gambardella, Gennaro, additional, Skinner, Alexandra, additional, Schjoldager, Katrine Ter-Borch Gram, additional, Beatson, Richard, additional, Graham, Rosalind, additional, Achkova, Daniela, additional, Taylor-Papadimitriou, Joyce, additional, Ciccarelli, Francesca D., additional, and Burchell, Joy M., additional

Published
2019
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43. O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR.

Author

Tajadura-Ortega, Virginia, Gambardella, Gennaro, Skinner, Alexandra, Halim, Adnan, Coillie, Julie Van, Schjoldager, Katrine Ter-Borch Gram, Beatson, Richard, Graham, Rosalind, Achkova, Daniela, Taylor-Papadimitriou, Joyce, Ciccarelli, Francesca D, and Burchell, Joy M

Subjects
EPIDERMAL growth factor receptors, MEMBRANE glycoproteins, GLYCOSYLATION, SIALYLTRANSFERASES, GENES, CATENINS, GLYCANS
Abstract

Aberrant mucin-type O-linked glycosylation is a common occurrence in cancer where the upregulation of sialyltransferases is often seen leading to the early termination of O-glycan chains. Mucin-type O-linked glycosylation is not limited to mucins and occurs on many cell surface glycoproteins including EGFR, where the number of sites can be limited. Upon EGF ligation, EGFR induces a signaling cascade and may also translocate to the nucleus where it directly regulates gene transcription, a process modulated by Galectin-3 and MUC1 in some cancers. Here, we show that upon EGF binding, breast cancer cells carrying different O-glycans respond by transcribing different gene expression signatures. MMP10, the principal gene upregulated when cells carrying sialylated core 1 glycans were stimulated with EGF, is also upregulated in ER-positive breast carcinoma reported to express high levels of ST3Gal1 and hence mainly core 1 sialylated O-glycans. In contrast, isogenic cells engineered to carry core 2 glycans upregulate CX3CL1 and FGFBP1 and these genes are upregulated in ER-negative breast carcinomas, also known to express longer core 2 O-glycans. Changes in O-glycosylation did not significantly alter signal transduction downstream of EGFR in core 1 or core 2 O-glycan expressing cells. However, striking changes were observed in the formation of an EGFR/galectin-3/MUC1/β-catenin complex at the cell surface that is present in cells carrying short core 1-based O-glycans but absent in core 2 carrying cells. [ABSTRACT FROM AUTHOR]

Published
2021
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44. Repurposing tin mesoporphyrin as a novel immune checkpoint therapy in the treatment of cancer: A preclinical evaluation.

Author

Arnold, James N., primary, Muliaditan, Tamara, additional, Opzoomer, James W., additional, Caron, Jonathan, additional, Okesola, Mary, additional, Kosti, Paris, additional, Lall, Sharanpreet, additional, Van Hemelrijck, Mieke, additional, Dazzi, Francesco, additional, Tutt, Andrew, additional, Grigoriadis, Anita, additional, Gillett, Cheryl, additional, Madden, Stephen F., additional, Burchell, Joy M, additional, Kordasti, Shahram, additional, Diebold, Sandra S., additional, and Spicer, James F., additional

Published
2018
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46. Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer

Author

Muliaditan, Tamara, primary, Opzoomer, James W., additional, Caron, Jonathan, additional, Okesola, Mary, additional, Kosti, Paris, additional, Lall, Sharanpreet, additional, Van Hemelrijck, Mieke, additional, Dazzi, Francesco, additional, Tutt, Andrew, additional, Grigoriadis, Anita, additional, Gillett, Cheryl E., additional, Madden, Stephen F., additional, Burchell, Joy M., additional, Kordasti, Shahram, additional, Diebold, Sandra S., additional, Spicer, James F., additional, and Arnold, James N., additional

Published
2018
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48. The breast cancer-associated glycoforms of MUC1, MUC1-Tn and sialyl-Tn, are expressed in COSMC wild-type cells and bind the C-type lectin MGL

Author

Beatson, Richard, Maurstad, Gjertrud, Picco, Gianfranco, Arulappu, Appitha, Coleman, Julia, Wandell, Hans H., Clausen, Henrik, Mandel, Ulla, Taylor-Papadimitriou, Joyce, Sletmoen, Marit, and Burchell, Joy M.

Subjects
Cell Line, Tumor, Mucin-1, lcsh:R, Humans, lcsh:Medicine, Antigens, Tumor-Associated, Carbohydrate, Breast Neoplasms, Female, Lectins, C-Type, lcsh:Q, lcsh:Science, Research Article, Protein Binding
Abstract

Aberrant glycosylation occurs in the majority of human cancers and changes in mucin-type O-glycosylation are key events that play a role in the induction of invasion and metastases. These changes generate novel cancer-specific glyco-antigens that can interact with cells of the immune system through carbohydrate binding lectins. Two glyco-epitopes that are found expressed by many carcinomas are Tn (GalNAc-Ser/Thr) and STn (NeuAcα2,6GalNAc-Ser/Thr). These glycans can be carried on many mucin-type glycoproteins including MUC1. We show that the majority of breast cancers carry Tn within the same cell and in close proximity to extended glycan T (Galβ1,3GalNAc) the addition of Gal to the GalNAc being catalysed by the T synthase. The presence of active T synthase suggests that loss of the private chaperone for T synthase, COSMC, does not explain the expression of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn can bind to the C-type lectin MGL and using atomic force microscopy show that they bind to MGL with a similar deadadhesion force. Tumour associated STn is associated with poor prognosis and resistance to chemotherapy in breast carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK activity. As engagement of MGL in the absence of TLR triggering may lead to anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the characteristics of STn expressing tumours. © 2015 Beatson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2015

49. The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9

Author

Beatson, Richard, primary, Tajadura-Ortega, Virginia, additional, Achkova, Daniela, additional, Picco, Gianfranco, additional, Tsourouktsoglou, Theodora-Dorita, additional, Klausing, Sandra, additional, Hillier, Matthew, additional, Maher, John, additional, Noll, Thomas, additional, Crocker, Paul R, additional, Taylor-Papadimitriou, Joyce, additional, and Burchell, Joy M, additional

Published
2016
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