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The Tim-3-Galectin-9 pathway and its regulatory mechanisms in human breast cancer

DOI: 10.3389/fimmu.2019.01594 DOI Help

Authors: Inna M. Yasinska (Universities of Kent and Greenwich) , Svetlana S. Sakhnevych (Universities of Kent and Greenwich) , Ludmila Pavlova (University of Essex) , Anette Teo Hansen Selnø (Universities of Kent and Greenwich) , Ana Maria Teuscher Abeleira (University of Bern; Biomedizinische Analytik HF) , Ouafa Benlaouer (Universities of Kent and Greenwich) , Isabel Gonçalves Silva (Universities of Kent and Greenwich) , Marianne Mosimann (University of Bern; Biomedizinische Analytik HF) , Luca Varani (Universita' della Svizzera italiana) , Marco Bardelli (Universita' della Svizzera italiana) , Rohanah Hussain (Diamond Light Source) , Giuliano Siligardi (Diamond Light Source) , Dietmar Cholewa (University of Bern) , Steffen M. Berger (University of Bern) , Bernhard F. Gibbs (Universities of Kent and Greenwich; University of Oldenburg) , Yuri A. Ushkaryov (Universities of Kent and Greenwich) , Elizaveta Fasler-Kan (University of Bern; University Hospital Basel; University of Basel) , Elena Klenova (University of Essex) , Vadim V. Sumbayev (Universities of Kent and Greenwich)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Frontiers In Immunology , VOL 10

State: Published (Approved)
Published: July 2019
Diamond Proposal Number(s): 20755

Open Access Open Access

Abstract: 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.

Journal Keywords: galectin-9; TIM-3; breast cancer; immune evasion; immune surveillance

Diamond Keywords: Breast Cancer

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: B23-Circular Dichroism

Added On: 15/07/2019 11:53


Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)