T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells

Sep 21, 2026

Uploaded by Theodora

T lymphocytes promote breast cancer cell penetration through the blood–brain barrier (BBB) by inducing tumor-cell protein changes. Using an in vitro BBB model, activated T cells or conditioned medium increased passage of three breast carcinoma cell lines, with weaker effects in the MDA-MB-231-B2M2 brain-affinity line. Liquid chromatography–mass spectrometry proteomics identified coronin-1A among significantly altered proteins. CORO1A knockdown reduced BBB crossing, and patient sample validation by immunohistochemistry and RT-PCR, supported by mRNA database analysis, linked CORO1A upregulation to cerebral metastasis potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Methods

Breast cancer cell lines

In vitro BBB model

Proteomics and protein knockdown

Validation in patient tissues and databases

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN T cell induced expression of Coronin-1A facilitates blood-brain barrier transmigration of breast cancer cells Johan M. Kros1􀀍, Lona Zeneyedpour2, Rute M. S. M. Pedrosa1, Zineb Belcaid1, Willem A. Dik3, Theo M. Luider2 & Dana A. M. Mustafa1 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 ofT 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. Keywords Breast cancer, Brain metastasis, Blood–brain barrier, Proteomics, Liquid chromatography-mass spectrometry, Coronin-1A Abbreviations BBB CM CORO1A coronin-1ADNA DMEM ECM ER Blood–brain barrier Conditioned medium Gene coding for the protein coronin-1 A Protein encoded by CORO1A Deoxyribonucleic acid Dulbecco modified eagle medium Endothelial cell medium Estrogen receptor 1Department of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Wytemaweg 80, 3000 DR Rotterdam, The Netherlands. 2Department of Neurology, Laboratory of Neuro‑Oncology, Clinical and Cancer Proteomics, Erasmus University Medical Center, Wytemaweg 80, 3000 DR Rotterdam, The Netherlands. 3Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Wytemaweg 80, 3000 DR Rotterdam, The Netherlands. 􀀍 [email: j. m.kros@erasmusmc.nl](email: j. m.kros@erasmusmc.nl) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) FFPE GEO HSAHCMDB HUVECLC-MS mRNA NCBI RNA ROI RPMIRT-PCR siRNATCGA Formalin-fixed paraffin-embedded Gene expression omnibus Human serum albumin Human cancer metastasis database Human umbilical vein endothelial cell Liquid chromatography-mass spectrometry Messenger RNA National Center for Biotechnology Information Ribonucleic acid Region of interest Roswell Park Memorial Institute ce

FAQs

What role do T lymphocytes play in breast cancer brain metastasis?

T lymphocytes facilitate breast cancer cell transmigration through the blood–brain barrier, thereby promoting the formation of brain metastases in ER-negative breast cancer contexts.

How was BBB passage measured in the study?

An in vitro BBB model was used to assess how activated T cells or their conditioned medium affect the passage of different breast cancer cell lines through the BBB.

Why is coronin-1A (CORO1A) important for BBB transmigration?

Mass spectrometry-based proteomics showed coronin-1A upregulation after T cell contact, and CORO1A knockdown significantly reduced the cancer cells’ ability to cross the artificial BBB.

Sep 21, 2026

Uploaded by Theodora