Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner.

Autor: Molostvov G; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Gachechiladze M; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Department of Clinical and Molecular Pathology, Palacky Univerzity, 7779 00 Olomouc, Czech Republic., Shaaban AM; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Hayward S; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Dean I; Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Dias IHK; Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK., Badr N; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt., Danial I; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Mohammed F; Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Novitskaya V; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., Paniushkina L; Faculty of Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, 79106 Freiburg, Germany., Speirs V; Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK; Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Hanby A; Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK., Nazarenko I; Faculty of Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, 79106 Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Withers DR; Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK., van Laere S; Translational Cancer Research Unit Center for Oncological Research, University Antwerp, Antwerp 2610, Belgium., Long HM; Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: h.m.long@bham.ac.uk., Berditchevski F; Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: f.berditchevski@bham.ac.uk.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2023 Mar 28; Vol. 42 (3), pp. 112207. Date of Electronic Publication: 2023 Mar 03.
DOI: 10.1016/j.celrep.2023.112207
Abstrakt: The immune microenvironment in breast cancer (BCa) is controlled by a complex network of communication between various cell types. Here, we find that recruitment of B lymphocytes to BCa tissues is controlled via mechanisms associated with cancer cell-derived extracellular vesicles (CCD-EVs). Gene expression profiling identifies the Liver X receptor (LXR)-dependent transcriptional network as a key pathway that controls both CCD-EVs-induced migration of B cells and accumulation of B cells in BCa tissues. The increased accumulation oxysterol ligands for LXR (i.e., 25-hydroxycholesterol and 27-hydroxycholesterol) in CCD-EVs is regulated by the tetraspanin 6 (Tspan6). Tspan6 stimulates the chemoattractive potential of BCa cells for B cells in an EV- and LXR-dependent manner. These results demonstrate that tetraspanins control intercellular trafficking of oxysterols via CCD-EVs. Furthermore, tetraspanin-dependent changes in the oxysterol composition of CCD-EVs and the LXR signaling axis play a key role in specific changes in the tumor immune microenvironment.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE