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

Guerman Molostvov, Mariam Gachechiladze, Abeer M. Shaaban, Steven Hayward, Isaac Dean, Irundika H.K. 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* (Corresponding Author), Fedor Berditchevski* (Corresponding Author)

*Corresponding author for this work

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Summary 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

We 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.


  • B cells
  • breast cancer
  • tumor microenvironment
  • tetraspanins
  • oxysterols
  • LXR


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