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

  • Yasinska IM Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Sakhnevych SS Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Pavlova L School of Biological Sciences, University of Essex, Colchester, United Kingdom.
  • Teo Hansen Selnø A Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Teuscher Abeleira AM Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Bern, Switzerland.
  • Benlaouer O Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Gonçalves Silva I Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Mosimann M Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Bern, Switzerland.
  • Varani L Institute for Research in Biomedicine, Universita' della Svizzera italiana, Bellinzona, Switzerland.
  • Bardelli M Institute for Research in Biomedicine, Universita' della Svizzera italiana, Bellinzona, Switzerland.
  • Hussain R Beamline B23, Diamond Light Source, Didcot, United Kingdom.
  • Siligardi G Beamline B23, Diamond Light Source, Didcot, United Kingdom.
  • Cholewa D Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Bern, Switzerland.
  • Berger SM Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Bern, Switzerland.
  • Gibbs BF Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Ushkaryov YA Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
  • Fasler-Kan E Department of Pediatric Surgery, Department of Biomedical Research, Children's Hospital, Inselspital, University of Bern, Bern, Switzerland.
  • Klenova E School of Biological Sciences, University of Essex, Colchester, United Kingdom.
  • Sumbayev VV Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United Kingdom.
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  • 2019-07-30
Published in:
  • Frontiers in immunology. - 2019
TIM-3
breast cancer
galectin-9
immune evasion
immune surveillance
Breast Neoplasms
Cell Line, Tumor
Female
Galectins
Hepatitis A Virus Cellular Receptor 2
Humans
Leukemia, Myeloid, Acute
MCF-7 Cells
Membrane Glycoproteins
Receptors, G-Protein-Coupled
Signal Transduction
T-Lymphocytes, Cytotoxic
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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/190734
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