scholarly journals RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ryo Sato ◽  
Teppei Nakano ◽  
Mari Hosonaga ◽  
Oltea Sampetrean ◽  
Ritsuko Harigai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Rna Sequencing ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Sequencing Analysis ◽  
Primary Tumors ◽  
The Brain

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

scholarly journals Loss of miR-101-3p Promotes Transmigration of Metastatic Breast Cancer Cells through the Brain Endothelium by Inducing COX-2/MMP1 Signaling

2020 ◽  
Vol 13 (7) ◽  
pp. 144 ◽  
Author(s):  
Rania Harati ◽  
Mohammad G. Mohammad ◽  
Abdelaziz Tlili ◽  
Raafat A. El-Awady ◽  
Rifat Hamoudi
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Metastatic Breast ◽  
Brain Endothelium ◽  
Cox 2 ◽  
The Brain

Brain metastases represent one of the incurable end stages in breast cancer (BC). Developing effective or preventive treatments is hampered by a lack of knowledge on the molecular mechanisms driving brain metastasis. Transmigration of BC cells through the brain endothelium is a key event in the pathogenesis of brain metastasis. In this study, we identified miR-101-3p as a critical micro-RNA able to reduce transmigration of BC cells through the brain endothelium. Our results revealed that miR-101-3p expression is downregulated in brain metastatic BC cells compared to less invasive variants, and varies inversely compared to the brain metastatic propensity of BC cells. Using a loss-and-gain of function approach, we found that miR-101-3p downregulation increased transmigration of BC cells through the brain endothelium in vitro by inducing COX-2 expression in cancer cells, whereas ectopic restoration of miR-101-3p exerted a metastasis-reducing effect. In regulatory experiments, we found that miR-101-3p mediated its effect by modulating COX-2-MMP1 signaling capable of degrading the inter-endothelial junctions (claudin-5 and VE-cadherin), key components of the brain endothelium. These findings suggest that miR-101-3p plays a critical role in the transmigration of breast cancer cells through the brain endothelium by modulating the COX-2-MMP1 signaling and thus may serve as a therapeutic target that can be exploited to prevent or suppress brain metastasis in human breast cancer.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals Molecular and cellular mechanisms underlying brain metastasis of breast cancer

2020 ◽  
Vol 39 (3) ◽  
pp. 711-720 ◽  
Author(s):  
Mari Hosonaga ◽  
Hideyuki Saya ◽  
Yoshimi Arima
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Breast Cancer Patients ◽  
Cellular Mechanisms ◽  
Her2 Positive ◽  
Cells Of The Microenvironment ◽  
The Brain

Abstract Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.

scholarly journals Dermatopontin is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that dermatopontin, encoded by DPT, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. We observed a significant correlation between DPT expression in primary tumors of the breast and overall survival. Molecular functions of dermatopontin may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of DPT may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals MPP6 is differentially expressed in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that membrane protein, palmitoylated 6 (MAGUK p55 subfamily member 6), encoded by MPP6, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. MPP6 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of MPP6 in primary tumors was correlated with patient overall survival in patients with breast cancer. Modulation of MPP6 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain.

scholarly journals BMS1, ribosome biogenesis factor pseudogene 20, (BMS1P20) is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Ribosome Biogenesis ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that BMS1, ribosome biogenesis factor pseudogene 20, encoded by BMS1P20, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of BMS1P20 may be relevant to the processes by which tumor cells of the breast metastasize to the brain. Down-regulation of BMS1P20 may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals Genetic mutations associated with lung cancer metastasis to the brain.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 41-41
Author(s):  
ChunXia Su ◽  
Juan Zhou ◽  
Xiangling Chu ◽  
Jing Zhao
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Genetic Alterations ◽  
Mapk Signaling ◽  
Primary Tumors ◽  
Cell Lung Carcinoma ◽  
The Brain

41 Background: Lung cancer is the most common cause of mortality in both men and women, accounting for one-quarter of all cancer deaths. Most lung cancer-associated deaths result from metastasis, especially brain metastasis. Metastasis associated mutations are important biomarkers for metastasis prediction and outcome improvement. The current study aimed to reveal the molecular mechanisms and the genetic alterations involved in metastasis from lung tumors to the brain. Methods: We carried out whole exome sequencing (WES) of the primary tumors and the corresponding brain metastases from 15 patients with metastatic non-small-cell lung carcinoma. Results: We identified novel lung cancer metastases associated genes (CHEK2P2, BAGE2, AHNAK2) and epigenetic factors (miR-4436A, miR-6077). Lung-brain metastasis samples have more similar Ti/Tv(transition/transversion) profile with brain cancer. Focal adhesion, PI3K-Akt signaling pathway, MAPK signaling pathway are some of the most important tumor onset and metastasis pathways. Alternative splicing, Methylation and EGF-like domain are important metabolic abnormal for the lung-metastasis cancers. Conclusions: We conducted a pairwise lung-brain metastasis based WES and identified some novel metastasis related mutations which provided potential biomarkers for prognosis and targeted therapeutics.

scholarly journals WISP2 is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Cells ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Down Regulation ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the WNT1 inducible signaling pathway protein 2, encoded by WISP2, was among the genes whose expression was most different in the metastatic tumor tissues of patients with metastatic breast cancer, both in metastases to brain and to the lymph nodes when compared to primary tumors of the breast or normal breast tissue, respectively. We observed significant down-regulation of WISP2 in metastasis to the brain. Decreased expression of WISP2 in breast cancer cells has been described to promote invasive and stem-like characteristics (6, 7). Molecular functions and down-regulation of WISP2 may be important for metastasis of primary tumor-derived cancer cells to the lymph nodes and to the brain in humans with metastatic breast cancer, and suggests some level of common origin for metastases that reside in the lymph nodes and colonize the brain.

scholarly journals Glucose Transporter 3 Is Essential for the Survival of Breast Cancer Cells in the Brain

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1568 ◽  
Author(s):  
Min-Hsun Kuo ◽  
Wen-Wei Chang ◽  
Bi-Wen Yeh ◽  
Yeh-Shiu Chu ◽  
Yueh-Chun Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Brain Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glucose Transporter ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

Breast cancer brain metastasis commonly occurs in one-fourth of breast cancer patients and is associated with poor prognosis. Abnormal glucose metabolism is found to promote cancer metastasis. Moreover, the tumor microenvironment is crucial and plays an active role in the metabolic adaptations and survival of cancer cells. Glucose transporters are overexpressed in cancer cells to increase glucose uptake. The glucose transporter 3 (GLUT3) is a high-affinity glucose transporter that is highly expressed in mammalian neurons. GLUT3 is also overexpressed in several malignant brain tumors. However, the role of GLUT3 in breast cancer brain metastasis remains unknown. The results of the present study demonstrated that GLUT3 is highly overexpressed in brain metastatic breast cancers and mediates glucose metabolic reprogramming. Furthermore, knockdown of cAMP-response element binding protein (CREB) could directly regulate GLUT3 expression in brain metastatic breast cancer cells. Notably, we verified and provided a novel role of GLUT3 in mediating glucose metabolism and assisting breast cancer cells to survive in the brain to promote brain metastasis.

scholarly journals BSCI-13. TUMOR-SPECIFIC tGLI1 TRANSCRIPTION FACTOR MEDIATES BREAST CANCER BRAIN METASTASIS VIA ACTIVATING METASTASIS-INITIATING CANCER STEM CELLS AND ASTROCYTES IN THE TUMOR MICROENVIRONMENT

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Sherona Sirkisoon ◽  
Richard Carpenter ◽  
Tadas Rimkus ◽  
Daniel Doheny ◽  
Dongqin Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Brain Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Tumor Type ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis

Abstract Breast cancer is the second leading cause of brain metastases in women; patients with breast cancer brain metastasis (BCBM) survive only 6–18 months after diagnosis. Mechanisms for BCBM remain unclear, which contributes to ineffective treatments and dismal prognosis. Truncated glioma-associated oncogene homolog 1 (tGLI1) belongs to the GLI1 family of zinc-finger transcription factors and functions as a tumor-specific gain-of-function mediator of tumor invasion and angiogenesis. Whether tGLI1 plays any role in metastasis of any tumor type remains unknown. Using an experimental metastasis mouse model, via intracardiac implantation, we showed that ectopic expression of tGLI1, but not GLI1, promoted preferential metastasis to brain. Conversely, selective tGLI1 knockdown using tGLI1-specific antisense oligonucleotides led to decreased brain metastasis of intracardially inoculated breast cancer cells. Furthermore, intracranial implantation mouse study revealed tGLI1 enhanced intracranial colonization and growth of breast cancer cells. Immunohistochemical staining of patient samples showed that tGLI1, but not GLI1, was increased in lymph node metastases compared to matched primary tumors, and that tGLI1 was expressed at higher levels in BCBM specimens compared to primary tumors. Whether tGLI1 plays any role in radioresistance is unknown; we found radioresistant BCBM cell lines and patient specimens expressed higher levels of tGLI1 than radiosensitive counterparts, and that tGLI1 promotes radioresistance. Since cancer stem cells (CSCs) are highly metastatic and radioresistant, we examined whether tGLI1 promotes BCBM and radioresistance through activating CSCs. Results showed that tGLI1 transcriptionally activates stemness genes CD44, Nanog, Sox2, and OCT4, leading to stem cell activation. Furthermore, we observed that tGLI1-positive CSCs strongly activated and interacted with astrocytes, the most abundant brain tumor microenvironmental cells known to promote tumor growth, in vitro and in vivo. Collectively, our findings establish a novel role of that tGLI1 plays in promoting breast cancer preferential metastasis to brain, radioresistance, and astrocytes in the metastatic niche.

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