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. & Long, H.
Medical Research Council
27/10/16 → 26/10/19
Project: Research Councils

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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.",

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

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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month = mar,

day = "28",

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

language = "English",

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journal = "Cell Reports",

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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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