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^* (Corresponding Author), Fedor Berditchevski^* (Corresponding Author)

^*Corresponding author for this work

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

Abstract

Summary 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	E-pub ahead of print - 3 Mar 2023

Keywords

B cells
breast cancer
tumor microenvironment
tetraspanins
oxysterols
LXR

UN SDGs

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

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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., Laere, S. V., 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), [112207]. https://doi.org/10.1016/j.celrep.2023.112207

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, Laere, SV, 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

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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 = "Summary 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, breast cancer, tumor microenvironment, tetraspanins, oxysterols, LXR",

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 Laere, {Steven van} and Long, {Heather M.} and Fedor Berditchevski",

note = "Acknowledgments We 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.",

year = "2023",

month = mar,

day = "3",

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

language = "English",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

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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 - Laere, Steven van

AU - Long, Heather M.

AU - Berditchevski, Fedor

N1 - Acknowledgments We 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.

PY - 2023/3/3

Y1 - 2023/3/3

N2 - Summary 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 - Summary 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 - breast cancer

KW - tumor microenvironment

KW - tetraspanins

KW - oxysterols

KW - LXR

U2 - 10.1016/j.celrep.2023.112207

DO - 10.1016/j.celrep.2023.112207

M3 - Article

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

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

Keywords

UN SDGs

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