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

Humans Female Liver X Receptors / metabolism Breast Neoplasms / genetics Oxysterols / pharmacology Tetraspanins B-Lymphocytes / metabolism Tumor Microenvironment
B cells CP: Cancer LXR breast cancer oxysterols tetraspanins tumor microenvironment

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
28 03 2023
Historique:
received: 06 06 2022
revised: 11 01 2023
accepted: 15 02 2023
medline: 3 4 2023
pubmed: 4 3 2023
entrez: 3 3 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2023.112207 PMID: 36867531
pubmed: 36867531
pii: S2211-1247(23)00218-8
doi: 10.1016/j.celrep.2023.112207
pii:
doi:

Substances chimiques

Liver X Receptors 0
Oxysterols 0
Tetraspanins 0
TSPAN6 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112207

Subventions

Organisme : Medical Research Council
ID : MR/N021738/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 099266/Z/12/Z
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Guerman Molostvov (G)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Mariam 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.

Abeer M Shaaban (AM)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Steven Hayward (S)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Isaac Dean (I)

Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Irundika H K Dias (IHK)

Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham B4 7ET, UK.

Nahla 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.

Irini Danial (I)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Fiyaz Mohammed (F)

Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Vera Novitskaya (V)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Liliia Paniushkina (L)

Faculty of Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, 79106 Freiburg, Germany.

Valerie 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.

Andrew Hanby (A)

Leeds Institute of Medical Research, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.

Irina 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.

David R Withers (DR)

Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Steven van Laere (S)

Translational Cancer Research Unit Center for Oncological Research, University Antwerp, Antwerp 2610, Belgium.

Heather M Long (HM)

Institute of Immunology and Immunotherapy, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: h.m.long@bham.ac.uk.

Fedor Berditchevski (F)

Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: f.berditchevski@bham.ac.uk.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs hépatiques X › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Lipides › Lipides membranaires › Stérols › Cholestérol › Oxystérols › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Tétraspanines › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Tspan6 stimulates the chemoattractive...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Tspan6 stimulates the chemoattractive...