Cell Reports (Mar 2023)

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,
  • Fedor Berditchevski

Journal volume & issue
Vol. 42, no. 3
p. 112207

Abstract

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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.

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