Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
27535
Cancer Research UK - United Kingdom
MR/N021738/1
Medical Research Council - United Kingdom
099266/Z/12/Z
Wellcome Trust - United Kingdom
PubMed
36867531
DOI
10.1016/j.celrep.2023.112207
PII: S2211-1247(23)00218-8
Knihovny.cz E-resources
- Keywords
- B cells, CP: Cancer, LXR, breast cancer, oxysterols, tetraspanins, tumor microenvironment,
- MeSH
- B-Lymphocytes metabolism MeSH
- Liver X Receptors metabolism MeSH
- Humans MeSH
- Tumor Microenvironment MeSH
- Breast Neoplasms * genetics MeSH
- Oxysterols * pharmacology MeSH
- Tetraspanins MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Liver X Receptors MeSH
- Oxysterols * MeSH
- Tetraspanins MeSH
- TSPAN6 protein, human MeSH Browser
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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