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

Guerman Molostov, Mariam Gachechiladze, Abeer M Shaaban, Steven Hayward, Isaac Dean, Irundika Dias, Nahla Badr, Irini Danial, Fiyaz Mohammed, Vera Novitskaya, Liliia Paniushkina, Valerie Speirs, Andrew Hanby, Irina Nazarenko, David R Withers, Steven van Laere, Heather M Long, Fedor Berditchevski

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number112207
Number of pages22
JournalCell Reports
Issue number3
Early online date3 Mar 2023
Publication statusPublished - 28 Mar 2023

Bibliographical note

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


  • B cells
  • CP: Cancer
  • LXR
  • breast cancer
  • oxysterols
  • tetraspanins
  • tumor microenvironment


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