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

Guerman Molostov; Mariam Gachechiladze; Abeer M Shaaban; Steven Hayward; Isaac Dean; Irundika 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 Molostov, Mariam Gachechiladze, Abeer M Shaaban, Steven Hayward, Isaac Dean, Irundika 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

Research output: Contribution to journal › Article › peer-review

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	22
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

Copyright © 2023. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Acknowledgments and Funding Information: The authors are grateful to Dr. O. Yoshie, Dr. E. Rubinstein, and Dr. S. Charrin for providing anti-tetraspanin mAbs. This work was supported by MRC grant (to F.B., A.M.S., and H.M.L.), the Inflammatory Breast Cancer Network UK (to F.B.), and Ministry of Higher Education and Research , Egypt (N.B.). A.M.S. is supported by the Birmingham CRUK Centre . I.H.K.D. acknowledges funding from Aston Medical School . F.M. is supported by Wellcome Trust grant 099266/Z/12/Z .

Publisher Copyright:
© 2023

Keywords

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

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10.1016/j.celrep.2023.112207Licence: CC BY-NC-ND 4.0

Molostovetal_2023_VoR
Copyright © 2023. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Final published version, 4.92 MBLicence: CC BY-NC-ND 4.0

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Molostov, G., Gachechiladze, M., Shaaban, A. M., Hayward, S., Dean, I., Dias, I., 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

@article{33c55ce43a7e4f10833893bed7861d80,

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 = "B cells, CP: Cancer, LXR, breast cancer, oxysterols, tetraspanins, tumor microenvironment",

author = "Guerman Molostov and Mariam Gachechiladze and Shaaban, {Abeer M} and Steven Hayward and Isaac Dean and Irundika Dias 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",

note = "Copyright {\textcopyright} 2023. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). Acknowledgments and Funding Information: The authors are grateful to Dr. O. Yoshie, Dr. E. Rubinstein, and Dr. S. Charrin for providing anti-tetraspanin mAbs. This work was supported by MRC grant (to F.B., A.M.S., and H.M.L.), the Inflammatory Breast Cancer Network UK (to F.B.), and Ministry of Higher Education and Research , Egypt (N.B.). A.M.S. is supported by the Birmingham CRUK Centre . I.H.K.D. acknowledges funding from Aston Medical School . F.M. is supported by Wellcome Trust grant 099266/Z/12/Z . Publisher Copyright: {\textcopyright} 2023",

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

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Molostov, G, Gachechiladze, M, Shaaban, AM, Hayward, S, Dean, I, Dias, I, 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 - Molostov, Guerman

AU - Gachechiladze, Mariam

AU - Shaaban, Abeer M

AU - Hayward, Steven

AU - Dean, Isaac

AU - Dias, Irundika

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

N1 - Copyright © 2023. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). Acknowledgments and Funding Information: The authors are grateful to Dr. O. Yoshie, Dr. E. Rubinstein, and Dr. S. Charrin for providing anti-tetraspanin mAbs. This work was supported by MRC grant (to F.B., A.M.S., and H.M.L.), the Inflammatory Breast Cancer Network UK (to F.B.), and Ministry of Higher Education and Research , Egypt (N.B.). A.M.S. is supported by the Birmingham CRUK Centre . I.H.K.D. acknowledges funding from Aston Medical School . F.M. is supported by Wellcome Trust grant 099266/Z/12/Z . Publisher Copyright: © 2023

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 - B cells

KW - CP: Cancer

KW - LXR

KW - breast cancer

KW - oxysterols

KW - tetraspanins

KW - tumor microenvironment

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DO - 10.1016/j.celrep.2023.112207

M3 - Article

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ER -

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

Abstract

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Keywords

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