scholarly journals CECR2 Drives Breast Cancer Metastasis by Suppressing Macrophage Inflammatory Responses

2020 ◽  
Author(s):  
Meiling Zhang ◽  
Zongzhi Z. Liu ◽  
Keisuke Aoshima ◽  
Yangyi Zhang ◽  
Yongyan An ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Inflammatory Responses ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Breast Cancer Metastasis ◽  
M2 Macrophages ◽  
Primary Tumors ◽  
Pharmacological Inhibition

AbstractEpigenetic and transcriptional changes are critical for metastasis, the major cause of cancer-related deaths. Metastatic tumor cells escape immune surveillance more efficiently than tumor cells in the primary sites, but the mechanisms controlling their immune evasion are poorly understood. We found that distal metastases are more immune inert with increased M2 macrophages compared to their matched primary tumors. Acetyl-lysine reader CECR2 is an epigenetic regulator upregulated in metastases and positively associated with M2 macrophages. CECR2 specifically promotes breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting. Mechanistically, NF-κB family member RELA recruits CECR2 to activate CSF1 and CXCL1, which are critical for macrophage-mediated immunosuppression at the metastatic sites. Furthermore, pharmacological inhibition of CECR2 bromodomain impedes NF-κB-mediated immune suppression by macrophages and inhibits breast cancer metastasis. These results reveal novel therapeutic strategies to treat metastatic breast cancer.Statement of SignificanceComparison of matched primary breast tumors and distal metastases show that metastases are more immune inert with increased tumor promoting macrophages. Depletion or pharmacological inhibition of CECR2 inhibits breast cancer metastasis by suppressing macrophage inflammatory responses, nominating CECR2 as a promising therapeutic target for cancer metastasis.

scholarly journals The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1909
Author(s):  
Tatiana S. Gerashchenko ◽  
Sofia Y. Zolotaryova ◽  
Artem M. Kiselev ◽  
Liubov A. Tashireva ◽  
Nikita M. Novikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Ether Lipid ◽  
Metastatic Tumor ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Breast Cancers ◽  
Invasive Component ◽  
Positive Expression

Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.

scholarly journals Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

2020 ◽  
Vol 21 (5) ◽  
pp. 1671 ◽  
Author(s):  
Anna Fabisiewicz ◽  
Malgorzata Szostakowska-Rodzos ◽  
Anna J. Zaczek ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Current Status ◽  
Molecular Profile ◽  
Breast Cancer Patients

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.

scholarly journals XCR1 is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Free Survival ◽  
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 the receptor for chemokines XCL1 and XCL2, the X-C motif chemokine receptor 1, encoded by XCR1, 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 (4). XCR1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). XCR1 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of XCR1 in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of XCR1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Breast Cancer Metastasis in the Skin with Hyperkeratotic Pigmentation Caused by Melanocyte Colonization

2018 ◽  
Vol 11 (3) ◽  
pp. 660-664
Author(s):  
Shino Ishihara-Yusa ◽  
Taku Fujimura ◽  
Chunbing Lyu ◽  
Masayuki Sugawara ◽  
Kazuhiro Sakamoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immunohistochemical Staining ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Rare Condition ◽  
Metastatic Tumor ◽  
Breast Cancer Metastasis ◽  
Keratinocyte Proliferation

Pigmented breast cancer in the skin caused by nonneoplastic melanocytes of epidermal origin is a rare condition of metastasis from breast cancer, but the pathogenesis of this phenomenon is almost unknown. In this report, we describe a case of breast cancer metastasis in the skin with prominent hyperkeratotic pigmentation caused by nonneoplastic melanocyte colonization. Immunohistochemical staining revealed that the metastatic tumor cells produced IL-23, which is reported not only to induce IL-17 but also to inhibit cell apoptosis in breast cancer cells, which affects tumor progression. In addition to IL-23, substantial numbers of IL-17-producing cells were detected at the peritumoral area, suggesting that IL-17 might induce not only melanogenesis but also keratinocyte proliferation and tumorigenesis. Our report suggests possible mechanisms of hyperkeratotic pigmentation of breast cancer metastasis in the skin.

scholarly journals FOXD2 is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Forkhead Box ◽  
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 the forkhead box D2, encoded by FOXD2, 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 (4). FOXD2 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). FOXD2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of FOXD2 in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of FOXD2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Secretagogin is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
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 secretagogin, encoded by SCGN, 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 (4). Secretagogin was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). SCGN mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SCGN in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of SCGN expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals ASZ1 is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Leucine Zipper ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Differentially Expressed ◽  
Basic Leucine Zipper ◽  
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 the ankyrin repeat, SAM and basic leucine zipper domain containing 1, encoded by ASZ1, 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 (4). ASZ1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). ASZ1 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ASZ1 in primary tumors was significantly correlated with patient post-progression survival. Modulation of ASZ1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals ERH is differentially expressed in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Free Survival ◽  
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 the enhancer of rudimentary homolog, encoded by ERH, 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 (4). ERH was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). ERH mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ERH in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of ERH expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Altered Expression of Secreted Mediator Genes That Mediate Aggressive Breast Cancer Metastasis to Distant Organs

2020 ◽  
Author(s):  
Aparna Maiti ◽  
Ichiro Okano ◽  
Masanori Oshi ◽  
Maiko Okano ◽  
Wanqing Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Primary Tumors ◽  
Altered Expression ◽  
Individual Gene ◽  
Metastatic Sites ◽  
Encoding Genes

Abstract Breast cancer most often recurs and metastasizes to the distal organs with their primary tumors surgically excised. Due to the heterogeneous nature of breast cancer, metastasis organotropism has poorly understood. This study assessed the specific cancer-related gene expression changes occurring with metastatic breast cancer recurrence to distant organs compared with non-metastatic breast cancer. We found that secreted mediators encoding genes (ANGPTL7, MMP3, LCN2, S100A8, and ESM1) are upregulated in primary breast tumors of 4T1.2, a highly metastatic variant of mouse triple-negative breast cancer (TNBC) 4T1 cells. Those genes are variably expressed at distant metastatic sites such as the spine, bone, and the lung in the syngeneic implantation/tumor-resection metastasis mouse model. The altered expression score of an individual gene was strongly associated with the survival of breast cancer patients. Notably, LCN2 and S100A8 overexpressed at the distant metastatic site spine (LCN2, 5 fold; S100A8, 6 fold) and bone (LCN2, 5 fold; S100A8, 3 fold) vs. primary tumors. In contrast, the ESM-1 encoding gene is overexpressed in the primary tumors and markedly downregulated at distant metastatic sites such as the spine, bone, and the lung. LCN2, S100A8, and ESM-1 mediators encoding individual gene expression scores were strongly associated with disease-specific survival (DSS) in the METABRIC cohort (hazard ratio [HR]>1, p < 0.0004). The gene expression scores predicted worse clinically aggressive tumors, such as high Nottingham histological grade and advanced cancer staging. High gene expression score of ESM-1 gene was strongly associated with worse overall survival (OS) in the triple-negative breast cancer (TNBC) and hormonal receptor (HR)-positive/Her2-negative subtype in METABRIC cohort, HER2+ subtype in TCGA-BRCA and SCAN-B breast cancer cohorts.Our data suggested that mediators encoding genes with both prognostic and predictive values may, therefore, be clinically useful for breast cancer spine, bone, and lung metastasis in particularly in more aggressive subtypes such as TNBC or HER2+ breast cancer.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
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 Rab11 family-interacting protein 4, encoded by RAB11FIP4, 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. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

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