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


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.

Publication DOI: https://doi.org/10.1016/j.celrep.2023.112207
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: Copyright © 2023. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). Acknowledgments and Funding Information: The authors are grateful to Dr. O. Yoshie, Dr. E. Rubinstein, and Dr. S. Charrin for providing anti-tetraspanin mAbs. This work was supported by MRC grant (to F.B., A.M.S., and H.M.L.), the Inflammatory Breast Cancer Network UK (to F.B.), and Ministry of Higher Education and Research , Egypt (N.B.). A.M.S. is supported by the Birmingham CRUK Centre . I.H.K.D. acknowledges funding from Aston Medical School . F.M. is supported by Wellcome Trust grant 099266/Z/12/Z . Publisher Copyright: © 2023
Uncontrolled Keywords: B cells,CP: Cancer,LXR,breast cancer,oxysterols,tetraspanins,tumor microenvironment,Biochemistry, Genetics and Molecular Biology(all)
Publication ISSN: 2211-1247
Last Modified: 23 May 2024 07:21
Date Deposited: 13 Mar 2023 11:15
Full Text Link:
Related URLs: https://www.cel ... Fshowall%3Dtrue (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2023-03-28
Published Online Date: 2023-03-03
Accepted Date: 2023-02-15
Authors: Molostov, Guerman
Gachechiladze, Mariam
Shaaban, Abeer M
Hayward, Steven
Dean, Isaac
Dias, Irundika (ORCID Profile 0000-0002-6620-8221)
Badr, Nahla
Danial, Irini
Mohammed, Fiyaz
Novitskaya, Vera
Paniushkina, Liliia
Speirs, Valerie
Hanby, Andrew
Nazarenko, Irina
Withers, David R
van Laere, Steven
Long, Heather M
Berditchevski, Fedor

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