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

doi:10.1016/j.celrep.2023.112207

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

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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.

Original language	English
Article number	112207
Number of pages	21
Journal	Cell Reports
Volume	42
Issue number	3
Early online date	3 Mar 2023
DOIs	https://doi.org/10.1016/j.celrep.2023.112207
Publication status	Published - 28 Mar 2023

Bibliographical note

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2023.112207Licence: Creative Commons: Attribution (CC BY)

Molostvov2023_Tspan6_StimulatesFinal published version, 4.93 MBLicence: Creative Commons: Attribution (CC BY)

Tspan6 as a regulator of immune microenvironment in breast cancer
Berditchevski, F. (Principal Investigator) & Long, H. (Co-Investigator)
Medical Research Council
27/10/16 → 26/10/19
Project: Research Councils

Cite this

Molostvov, G., Gachechiladze, M., Shaaban, A. M., Hayward, S., Dean, I., Dias, I. H. K., Badr, N., Danial, I., Mohammed, F., Novitskaya, V., Paniushkina, L., Speirs, V., Hanby, A., Nazarenko, I., Withers, D. R., van Laere, S., Long, H. M., & Berditchevski, F. (2023). Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner. Cell Reports, 42(3), Article 112207. https://doi.org/10.1016/j.celrep.2023.112207

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

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.",

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author = "Guerman Molostvov and Mariam Gachechiladze and Shaaban, {Abeer M} and Steven Hayward and Isaac Dean and Dias, {Irundika H K} and Nahla Badr and Irini Danial and Fiyaz Mohammed and Vera Novitskaya and Liliia Paniushkina and Valerie Speirs and Andrew Hanby and Irina Nazarenko and Withers, {David R} and {van Laere}, Steven and Long, {Heather M} and Fedor Berditchevski",

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doi = "10.1016/j.celrep.2023.112207",

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Molostvov, G, Gachechiladze, M, Shaaban, AM, Hayward, S, Dean, I, Dias, IHK, Badr, N, Danial, I, Mohammed, F, Novitskaya, V, Paniushkina, L, Speirs, V, Hanby, A, Nazarenko, I, Withers, DR, van Laere, S, Long, HM & Berditchevski, F 2023, 'Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner', Cell Reports, vol. 42, no. 3, 112207. https://doi.org/10.1016/j.celrep.2023.112207

TY - JOUR

T1 - Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner

AU - Molostvov, Guerman

AU - Gachechiladze, Mariam

AU - Shaaban, Abeer M

AU - Hayward, Steven

AU - Dean, Isaac

AU - Dias, Irundika H K

AU - Badr, Nahla

AU - Danial, Irini

AU - Mohammed, Fiyaz

AU - Novitskaya, Vera

AU - Paniushkina, Liliia

AU - Speirs, Valerie

AU - Hanby, Andrew

AU - Nazarenko, Irina

AU - Withers, David R

AU - van Laere, Steven

AU - Long, Heather M

AU - Berditchevski, Fedor

PY - 2023/3/28

Y1 - 2023/3/28

N2 - 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.

AB - 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.

KW - Humans

KW - Female

KW - Liver X Receptors/metabolism

KW - Breast Neoplasms/genetics

KW - Oxysterols/pharmacology

KW - Tetraspanins

KW - B-Lymphocytes/metabolism

KW - Tumor Microenvironment

U2 - 10.1016/j.celrep.2023.112207

DO - 10.1016/j.celrep.2023.112207

M3 - Article

C2 - 36867531

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 112207

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Tspan6 as a regulator of immune microenvironment in breast cancer

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