miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-α

Abstract In previous work, we showed the prominence of the T cell response in the formation of brain metastases of primary ER-negative breast cancers. We also showed that prior co-cultured breast cancer cells with stimulated T lymphocytes bear an overexpression of Guanylate-binding protein 1 (GBP1) and possess an increased trespassing ability through an in vitro blood-brain barrier (BBB) model. In addition, we demonstrated a predilection for metastasizing to the brain of breast cancer cells that were co-cultured with activated T cells in a mouse model. In the present work, we show that activated CD8+ cytotoxic T lymphocytes, rather than CD4+ lymphocytes, are the main cause of increasing the ability of breast cancer cells to cross the BBB. While synthetic IFNγ does not change the ability of breast cancer cells to cross the BBB, this study shows that the T lymphocyte-secreted IFNγ activates the STAT1-dependent IFNγ pathway in breast cancer cells, enabling them to cross the in vitro BBB. Direct inhibition of soluble IFNγ or blocking of the IFNγ-specific receptor in breast cancer cells significantly decreases their ability to cross the BBB. The results illustrate that IFNγ signaling pathway is one of the crucial pathways in the formation of brain metastasis of ER- breast cancer. The interference with the IFNγ pathway will develop preventive strategies against the formation of brain metastases of breast cancer.

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The inhibitory effects of butein on cell proliferation and TNF-α-induced CCL2 release in racially different triple negative breast cancer cells

PLoS ONE ◽

10.1371/journal.pone.0215269 ◽

2019 ◽

Vol 14 (10) ◽

pp. e0215269

Author(s):

Patricia Mendonca ◽

Ainsley Horton ◽

David Bauer ◽

Samia Messeha ◽

Karam F. A. Soliman

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Inhibitory Effects ◽

Tnf Α

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Stable Spontaneous Fusion of Estrogen Receptor (ER) Positive and ER Negative Breast Cancer Cells Generates an Efficient Model for Breast Cancer Brain Metastasis.

10.1158/0008-5472.sabcs-09-6147 ◽

2009 ◽

Author(s):

K. De ◽

A. Bandyopadhyay ◽

A. Chang ◽

A. Elkahloun ◽

J. Cornell ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Brain Metastasis ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Breast Cancer Brain Metastasis ◽

Er Positive

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Abstract 5161: Cell mechanics-cytoskeleton-membrane protein transduction loop mediates brain metastasis of breast cancer cells

10.1158/1538-7445.am2011-5161 ◽

2011 ◽

Author(s):

Hong Zhao ◽

Fang Nie ◽

Kemi Cui ◽

Zhongcheng Gong ◽

Siva Penmnesta ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Membrane Protein ◽

Cancer Cells ◽

Cell Mechanics ◽

Breast Cancer Cells ◽

Protein Transduction

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HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway

Cells ◽

10.3390/cells9051280 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1280

Author(s):

Seung-Ho Park ◽

Hyunhee Kim ◽

Sungmin Kwak ◽

Ji-Hoon Jeong ◽

Jangho Lee ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Tnf Α ◽

Mcf 7

Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3–ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3–ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3–ERα complex and substitution of the occupancy on the promoter by the p53–p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3–ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies.

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HIF-1α Acts Downstream of TNF-α to Inhibit Vasodilator-Stimulated Phosphoprotein Expression and Modulates the Adhesion and Proliferation of Breast Cancer Cells

DNA and Cell Biology ◽

10.1089/dna.2011.1563 ◽

2012 ◽

Vol 31 (6) ◽

pp. 1078-1087 ◽

Cited By ~ 11

Author(s):

Ke Su ◽

Yihao Tian ◽

Jing Wang ◽

Wentao Shi ◽

Daji Luo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Tnf Α

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Preliminary characterization of an experimental breast cancer cells brain metastasis mouse model by MRI/MRS

Magnetic Resonance Materials in Physics Biology and Medicine ◽

10.1007/s10334-008-0114-6 ◽

2008 ◽

Vol 21 (4) ◽

pp. 237-249 ◽

Cited By ~ 16

Author(s):

R. V. Simões ◽

A. Martinez-Aranda ◽

B. Martín ◽

S. Cerdán ◽

A. Sierra ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Mouse Model ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Preliminary Characterization

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Exosomes Derived from Brain Metastatic Breast Cancer Cells Destroy the Blood-Brain Barrier by Carrying lncRNA GS1-600G8.5

BioMed Research International ◽

10.1155/2020/7461727 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yunhe Lu ◽

Lei Chen ◽

Liangdong Li ◽

Yiqun Cao

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Brain Metastasis ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Metastatic Breast ◽

Metastatic Cells

Brain metastasis is a major cause of death in breast cancer patients. The greatest event for brain metastasis is the breaching of the blood-brain barrier (BBB) by cancer cells. The role of exosomes in cancer metastasis is clear, whereas the role of exosomes in the integrity of the BBB is unknown. Here, we established a highly brain metastatic breast cancer cell line by three cycles of in vivo selection. The effect of exosomes on the BBB was evaluated in vitro by tracking, transepithelial/transendothelial electrical resistance (TEER), and permeability assays. BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the GEO dataset and verified by real-time PCR, TEER, permeability, and Transwell assays. The cells obtained by the in vivo selection showed higher brain metastatic capacity in vivo and higher migration and invasion in vitro compared to the parental cells. Exosomes from the highly brain metastatic cells were internalized by brain microvascular endothelial cells (BMECs), which reduced TEER and increased permeability of BBB. The exosomes derived from the highly metastatic cells promoted invasion of the breast cancer cells in the BBB model. lncRNA GS1-600G8.5 was highly expressed in the highly brain metastatic cells and their exosomes, as compared to the samples with reduced metastatic behavior. Silencing of GS1-600G8.5 significantly abrogated the BBB destructive effect of exosomes. GS1-600G8.5-deficient exosomes failed to promote the infiltration of cancer cells through the BBB. Furthermore, BMECs treated with GS1-600G8.5-deprived exosomes expressed higher tight junction proteins than those treated with the control exosomes. These data suggest the exosomes derived from highly brain metastatic breast cancer cells might destroy the BBB system and promote the passage of cancer cells across the BBB, by transferring lncRNA GS1-600G8.5.

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