Dataset Information

T Lymphocytes induce the expression of Coronin-1A in breast cancer cells enabling the transmigration through a blood-brain-barrier model

ABSTRACT: Background: 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 expressional changes due to T cell contact associated with penetration through the BBB for breast cancer cell lines derived from cancers with various affinities for brain. Methods: Differential expression of proteins was identified by comparing the proteomes of the breast cancer cells before and after co-culture with T cells by using liquid chromatography-mass spectrometry (LC-MS). siRNA was used to silence protein expression in the tumor cells and the artificial BBB model was employed to study the effects on passage of the breast carcinoma cell lines. Results: 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-1A, 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. Conclusions: We conclude that T lymphocytes trigger cancer cells to express proteins including coronin-1A thereby facilitating their passage through 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Lona Zeneyedpour

LAB HEAD: Theo Luider

PROVIDER: PXD053787 | Pride | 2025-02-24

REPOSITORIES: pride

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			Action	DRS
	170420OFc1_RP-1437-B2M2-INF-R1_C026.raw	Raw
	170420OFc1_RP-1437-B2M2-INF-R1_C026__F129735_.mzid.gz	Mzid
	170420OFc1_RP-1437-B2M2-INF-R1_C026__F129735_.mzid_170420OFc1_RP-1437-B2M2-INF-R1_C026__F129735_.MGF	Mzid
	170421OFc1_RP-1437-B2M2-R1_C010.raw	Raw
	170421OFc1_RP-1437-B2M2-R1_C010__F129741_.mzid.gz	Mzid

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

Kros Johan M JM Zeneyedpour Lona L Pedrosa Rute M S M RMSM Belcaid Zineb Z Dik Willem A WA Luider Theo M TM Mustafa Dana A M DAM

Scientific reports 20241228 1

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 c ...[more]

PMID: 39733107

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