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The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer

  • Yasinska, Inna M. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • Sakhnevych, Svetlana S. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • Pavlova, Ludmila School of Biological Sciences, University of Essex, United Kingdom
  • Hansen Selnø, Anette Teo Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • 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
  • Benlaouer, Ouafa Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • Gonçalves Silva, Isabel Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • 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
  • Varani, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Bardelli, Marco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Hussain, Rohanah Beamline B23, Diamond Light Source, United Kingdom
  • Siligardi, Giuliano Beamline B23, Diamond Light Source, United Kingdom
  • Cholewa, Dietmar Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
  • Berger, Steffen M. Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Switzerland
  • Gibbs, Bernhard F. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom - Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Germany
  • Ushkaryov, Yuri A. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
  • 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
  • Klenova, Elena School of Biological Sciences, University of Essex, Colchester, United Kingdom
  • Sumbayev, Vadim V. Medway School of Pharmacy, Universities of Kent and Greenwich, United Kingdom
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    11.07.2019
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  • Frontiers in immunology. - 2019, vol. 10, p. 1594
Galectin-9
TIM-3
Breast cancer
Immune evasion
Immune surveillance
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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  • English
Classification
Pathology, clinical medicine
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https://n2t.net/ark:/12658/srd1319080
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