T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells
Abstract In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored how T lymphocytes promote breast cancer cell penetration through the blood brain barrier (BBB). An in vitro BBB model was e...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-83301-x |
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| author | Johan M. Kros Lona Zeneyedpour Rute M. S. M. Pedrosa Zineb Belcaid Willem A. Dik Theo M. Luider Dana A. M. Mustafa |
| author_facet | Johan M. Kros Lona Zeneyedpour Rute M. S. M. Pedrosa Zineb Belcaid Willem A. Dik Theo M. Luider Dana A. M. Mustafa |
| author_sort | Johan M. Kros |
| collection | DOAJ |
| description | Abstract In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored how T lymphocytes promote breast cancer cell penetration through the blood brain barrier (BBB). An in vitro BBB model was employed to study the effects of T lymphocytes on BBB trespassing capacity of three different breast carcinoma cell lines. Differential protein expression was explored by comparing the proteomes of the breast cancer cells before and after co-culture with activated T lymphocytes using liquid chromatography-mass spectrometry (LC-MS). siRNA was used to silence protein expression in the breast cancer cells to study contribution to in vitro BBB passage. Furthermore, protein expression in primary breast cancer tissues was explored and related to brain-metastatic potential. Co-culturing with activated T lymphocytes or their conditioned medium (CM) resulted in increased passage through the in vitro BBB. The effects were less for cell line MDA-MB-231-B2M2 (brain affinity) as compared to MDA-MB-231 and SK-BR-7. Mass spectrometry-based proteomics revealed significant alterations in the expression of 35 proteins by the breast cancer cell lines upon T cell contact. Among the proteins is coronin-1 A, a protein related to cell motility. Knockdown of CORO1A in the breast cancer cells reduced their ability to cross the artificial BBB to 60%. The effects were significantly less for the cell line derived from breast cancer with affinity for brain. The expression of coronin-1A was confirmed by immunohistochemistry and RT-PCR of 52 breast cancer samples of patients with metastasized breast cancers, with and without brain locations. Lastly, CORO1A upregulation was validated in a publicly available mRNA expression database from 204 primary breast cancers with known metastatic sites. We conclude that T lymphocytes trigger cancer cells to express proteins including coronin-1A that enable the cancer cells to cross an in vitro BBB. In addition, a prominent role of coronin-1A in the formation of cerebral metastases in breast cancer patients is strongly suggestive by its upregulation in tissue samples of breast cancer patients with brain metastases. |
| format | Article |
| id | doaj-art-68cabac9c50f4016a776e0a3b64a3786 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-68cabac9c50f4016a776e0a3b64a37862024-12-29T12:16:59ZengNature PortfolioScientific Reports2045-23222024-12-0114111410.1038/s41598-024-83301-xT cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cellsJohan M. Kros0Lona Zeneyedpour1Rute M. S. M. Pedrosa2Zineb Belcaid3Willem A. Dik4Theo M. Luider5Dana A. M. Mustafa6Department of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical CenterDepartment of Neurology, Laboratory of Neuro‑Oncology, Clinical and Cancer Proteomics, Erasmus University Medical CenterDepartment of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical CenterDepartment of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical CenterLaboratory Medical Immunology, Department of Immunology, Erasmus University Medical CenterDepartment of Neurology, Laboratory of Neuro‑Oncology, Clinical and Cancer Proteomics, Erasmus University Medical CenterDepartment of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical CenterAbstract In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored how T lymphocytes promote breast cancer cell penetration through the blood brain barrier (BBB). An in vitro BBB model was employed to study the effects of T lymphocytes on BBB trespassing capacity of three different breast carcinoma cell lines. Differential protein expression was explored by comparing the proteomes of the breast cancer cells before and after co-culture with activated T lymphocytes using liquid chromatography-mass spectrometry (LC-MS). siRNA was used to silence protein expression in the breast cancer cells to study contribution to in vitro BBB passage. Furthermore, protein expression in primary breast cancer tissues was explored and related to brain-metastatic potential. Co-culturing with activated T lymphocytes or their conditioned medium (CM) resulted in increased passage through the in vitro BBB. The effects were less for cell line MDA-MB-231-B2M2 (brain affinity) as compared to MDA-MB-231 and SK-BR-7. Mass spectrometry-based proteomics revealed significant alterations in the expression of 35 proteins by the breast cancer cell lines upon T cell contact. Among the proteins is coronin-1 A, a protein related to cell motility. Knockdown of CORO1A in the breast cancer cells reduced their ability to cross the artificial BBB to 60%. The effects were significantly less for the cell line derived from breast cancer with affinity for brain. The expression of coronin-1A was confirmed by immunohistochemistry and RT-PCR of 52 breast cancer samples of patients with metastasized breast cancers, with and without brain locations. Lastly, CORO1A upregulation was validated in a publicly available mRNA expression database from 204 primary breast cancers with known metastatic sites. We conclude that T lymphocytes trigger cancer cells to express proteins including coronin-1A that enable the cancer cells to cross an in vitro BBB. In addition, a prominent role of coronin-1A in the formation of cerebral metastases in breast cancer patients is strongly suggestive by its upregulation in tissue samples of breast cancer patients with brain metastases.https://doi.org/10.1038/s41598-024-83301-xBreast cancerBrain metastasisBlood–brain barrierProteomicsLiquid chromatography-mass spectrometryCoronin-1A |
| spellingShingle | Johan M. Kros Lona Zeneyedpour Rute M. S. M. Pedrosa Zineb Belcaid Willem A. Dik Theo M. Luider Dana A. M. Mustafa T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells Scientific Reports Breast cancer Brain metastasis Blood–brain barrier Proteomics Liquid chromatography-mass spectrometry Coronin-1A |
| title | T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells |
| title_full | T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells |
| title_fullStr | T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells |
| title_full_unstemmed | T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells |
| title_short | T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells |
| title_sort | t cell induced expression of coronin 1a facilitates blood brain barrier transmigration of breast cancer cells |
| topic | Breast cancer Brain metastasis Blood–brain barrier Proteomics Liquid chromatography-mass spectrometry Coronin-1A |
| url | https://doi.org/10.1038/s41598-024-83301-x |
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