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

Cell Rep. 2023 Mar 28;42(3):112207. doi: 10.1016/j.celrep.2023.112207. Epub 2023 Mar 3.

Abstract

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.

Keywords: B cells; CP: Cancer; LXR; breast cancer; oxysterols; tetraspanins; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Breast Neoplasms* / genetics
  • Female
  • Humans
  • Liver X Receptors / metabolism
  • Oxysterols* / pharmacology
  • Tetraspanins
  • Tumor Microenvironment

Substances

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