The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer
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Yasinska, Inna M.
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Sakhnevych, Svetlana S.
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Pavlova, Ludmila
School of Biological Sciences, University of Essex, United Kingdom
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Hansen Selnø, Anette Teo
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Teuscher Abeleira, Ana Maria
Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Zentrum Für Medizinische Bildung, Biomedizinische Analytik HF, Switzerland
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Benlaouer, Ouafa
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Gonçalves Silva, Isabel
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Mosimann, Marianne
Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Zentrum Für Medizinische Bildung, Biomedizinische Analytik HF, Switzerland
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Varani, Luca
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Bardelli, Marco
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Hussain, Rohanah
Beamline B23, Diamond Light Source, United Kingdom
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Siligardi, Giuliano
Beamline B23, Diamond Light Source, United Kingdom
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Cholewa, Dietmar
Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
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Berger, Steffen M.
Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
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Gibbs, Bernhard F.
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Germany
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Ushkaryov, Yuri A.
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Fasler-Kan, Elizaveta
Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland - Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland
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Klenova, Elena
School of Biological Sciences, University of Essex, Colchester, United Kingdom
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Sumbayev, Vadim V.
Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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Published in:
- Frontiers in immunology. - 2019, vol. 10, p. 1594
English
Human cancer cells operate a variety of effective molecular and signaling mechanisms which allow them to escape host immune surveillance and thus progress the disease. We have recently reported that the immune receptor Tim-3 and its natural ligand galectin-9 are involved in the immune escape of human acute myeloid leukemia (AML) cells. These cells use the neuronal receptor latrophilin 1 (LPHN1) and its ligand fibronectin leucine rich transmembrane protein 3 (FLRT3, and possibly other ligands) to trigger the pathway. We hypothesized that the Tim-3-galectin-9 pathway may be involved in the immune escape of cancer cells of different origins. We found that studied breast tumors expressed significantly higher levels of both galectin-9 and Tim-3 compared to healthy breast tissues of the same patients and that these proteins were co-localized. Increased levels of LPHN2 and expressions of LPHN3 as well as FLRT3 were also detected in breast tumor cells. Activation of this pathway facilitated the translocation of galectin-9 onto the tumor cell surface, however no secretion of galectin-9 by tumor cells was observed. Surface-based galectin-9 was able to protect breast carcinoma cells against cytotoxic T cell-induced death. Furthermore, we found that cell lines from brain, colorectal, kidney, blood/mast cell, liver, prostate, lung, and skin cancers expressed detectable amounts of both Tim-3 and galectin- 9 proteins. The majority of cell lines expressed one of the LPHN isoforms and FLRT3. We conclude that the Tim-3-galectin-9 pathway is operated by a wide range of human cancer cells and is possibly involved in prevention of anti-tumor immunity.
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Pathology, clinical medicine
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License undefined
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https://n2t.net/ark:/12658/srd1319080
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