scholarly journals Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis

2018 ◽  
Vol 11 (7) ◽  
pp. DMM034850 ◽  
Author(s):  
Soo-Hyun Kim ◽  
Richard P. Redvers ◽  
Lap Hing Chi ◽  
Xiawei Ling ◽  
Andrew J. Lucke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Relevant Model ◽  
Breast Cancer Brain Metastasis ◽  
Therapeutic Evaluation

scholarly journals Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis

2018 ◽  
Author(s):  
Soo-Hyun Kim ◽  
Richard P. Redvers ◽  
Lap Hing Chi ◽  
Xiawei Ling ◽  
Andrew J. Lucke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Brain Metastasis ◽  
Histone Deacetylase ◽  
Clinical Relevance ◽  
Histone Deacetylase Inhibitors ◽  
Novel Therapies ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

ABSTRACTBreast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. By immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain. In vitro assays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain-selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sites in vivo and potent radio-sensitising properties in vitro. The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis.SUMMARY STATEMENTWe introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis and test novel therapies.

Emerging Drugs for the Treatment of Breast Cancer Brain Metastasis: A Review of Patent Literature

2018 ◽  
Vol 13 (3) ◽  
pp. 348-359 ◽  
Author(s):  
Maricruz Anaya-Ruiz ◽  
Cindy Bandala ◽  
Patricia Martinez-Morales ◽  
Gerardo Landeta ◽  
Rebeca D. Martinez-Contreras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Breast Cancer Brain Metastasis ◽  
Patent Literature

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

scholarly journals Application of fluorescein sodium in breast cancer brain-metastasis surgery

2018 ◽  
Vol Volume 10 ◽  
pp. 4325-4331 ◽  
Author(s):  
Shi-yin Xiao ◽  
Ji Zhang ◽  
Zheng-quan Zhu ◽  
You-ping Li ◽  
Wei-ying Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Fluorescein Sodium ◽  
Breast Cancer Brain Metastasis

scholarly journals JAK2-binding long noncoding RNA promotes breast cancer brain metastasis

2017 ◽  
Vol 127 (12) ◽  
pp. 4498-4515 ◽  
Author(s):  
Shouyu Wang ◽  
Ke Liang ◽  
Qingsong Hu ◽  
Ping Li ◽  
Jian Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Brain Metastasis

scholarly journals CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

2020 ◽  
Author(s):  
Bo Fu ◽  
Wei Liu ◽  
Peng Li ◽  
Li Pan ◽  
Ke Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Tumorigenesis And Progression ◽  
And Migration

Abstract Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

Aging and CNS myeloid cell depletion attenuate breast cancer brain metastasis

2021 ◽  
pp. clincanres.CCR-21-1549-A.2021
Author(s):  
Alex Man Lai Wu ◽  
Selamawit Gossa ◽  
Ramakrishna Samala ◽  
Monika A. Chung ◽  
Brunilde Gril ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Myeloid Cell ◽  
Cell Depletion ◽  
Breast Cancer Brain Metastasis
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