scholarly journals Relation between Immune cell response and stemness genes expression in breast cancer; A new approach in NANOG gene and Let7-a expression in breast cancer cell lines

2020 ◽  
Vol 6 (2) ◽  
pp. e21-e21
Author(s):  
Zeynab Aliyari-Serej ◽  
Ayyub Ebrahimi ◽  
Tohid Kazemi ◽  
Souzan Najafi ◽  
Elmira Roshani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Preclinical Study ◽  
Breast Cancer Cell Lines ◽  
Developmental Behavior ◽  
Genes Expression ◽  
Nanog Gene ◽  
Immune Cell Response

Introduction: Failure and recurrence in breast cancer treatment cause a great obstacle in cancer therapy and identification of cell population named cancer stem cells (CSCs) in the tumor can be led us to define it as target in novel therapeutic strategy. Objectives: The aim of this study is the finding of correlation between stemness and metastatic characteristic, also knowing CSCs as a potential target of therapy because of its developmental behavior and similarities with normal stem cells. Materials and Methods: Here, we focus on the expression of NANOG in breast CSCs, a key molecule in the physiological process of stem cells and the Let-7a that is involved in the differentiation of the cells. Results: In this work, we found that NANOG was highly expressed in SKBR3 and down-regulation of let-7a, as a differentiation miRNA, was found in MDA-MB-468 cells. Conclusion: It will be critical for the developing of effective anti-tumor drugs, utilizing mentioned concepts. Inhibition of NANOG in combination with Let-7a up-regulation can help to decrease the stemness and increase the differentiation of CSCs. The decrease of stemness and increase of differentiation initiate the apoptotic process. So, modification in the mechanism of apoptosis beside anti-cancer drugs provide a good preclinical study goal. However, in order to these drugs become clinical, the problems of their side effects and toxicity must be solved. Differentiation of CSCs provides an optimal condition to activity of immune cells which never let them escape from immune cells by alteration of immunogenicity.

scholarly journals Correlation Between 18F-FDG Uptake and Immune Cell Infiltration in Metastatic Brain Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Young-Sil An ◽  
Se-Hyuk Kim ◽  
Tae Hoon Roh ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Standardized Uptake Value ◽  
Brain Lesions ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Ki 67 ◽  
Glucose Transporter 1 ◽  
Fdg Uptake

BackgroundThe purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.MethodsThis retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.ResultsThe degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.ConclusionsIn metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.

scholarly journals Erratum: Corrigendum: Bub1 is required for maintaining cancer stem cells in breast cancer cell lines

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jeong Yoon Han ◽  
Yu Kyeong Han ◽  
Ga-Young Park ◽  
Sung Dae Kim ◽  
Chang Geun Lee
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

scholarly journals The Chemokine Receptor CXCR3 Isoform B Drives Breast Cancer Stem Cells

2019 ◽  
Vol 13 ◽  
pp. 117822341987362 ◽  
Author(s):  
Namita Kundu ◽  
Xinrong Ma ◽  
Regine Brox ◽  
Xiaoxuan Fan ◽  
Tyler Kochel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cell ◽  
Cell Population ◽  
Chemokine Receptor ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Tumor Cell Population ◽  
Isoform B

We are seeking to identify molecular targets that are relevant to breast cancer cells with stem-like properties. There is growing evidence that cancer stem cells (CSCs) are supported by inflammatory mediators expressed in the tumor microenvironment. The chemokine receptor CXCR3 binds the interferon-γ-inducible, ELR-negative CXC chemokines CXCL9, CXCL10, and CXCL11 and malignant cells have co-opted this receptor to promote tumor cell migration and invasion. There are 2 major isoforms of CXCR3: CXCR3A and CXCR3B. The latter is generated from alternative splicing and results in a protein with a longer N-terminal domain. CXCR3 isoform A is generally considered to play a major role in tumor metastasis. When the entire tumor cell population is examined, CXCR3 isoform B is usually detected at much lower levels than CXCR3A and for this, and other reasons, was not considered to drive tumor progression. We have shown that CXCR3B is significantly upregulated in the subpopulation of breast CSCs in comparison with the bulk tumor cell population in 3 independent breast cancer cell lines (MDA-MB-231, SUM159, and T47D). Modulation of CXCR3B levels by knock in strategies increases CSC populations identified by aldehyde dehydrogenase activity or CD44+CD24− phenotype as well as tumorsphere-forming capacity. The reverse is seen when CXCR3B is gene-silenced. CXCL11 and CXCL10 directly induce CSC. We also report that novel CXCR3 allosteric modulators BD064 and BD103 prevent the induction of CSCs. BD103 inhibited experimental metastasis. This protective effect is associated with the reversal of CXCR3 ligand-mediated activation of STAT3, ERK1/2, CREB, and NOTCH1 pathways. We propose that CXCR3B, expressed on CSC, should be explored further as a novel therapeutic target.

scholarly journals MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
G. K. Chimal-Ramírez ◽  
N. A. Espinoza-Sánchez ◽  
D. Utrera-Barillas ◽  
L. Benítez-Bribiesca ◽  
J. R. Velázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Cells ◽  
Immune Cell ◽  
Morphological Changes ◽  
Tumor Stroma ◽  
Collagen Degradation ◽  
Tumor Aggressiveness ◽  
Soluble Factors ◽  
Immune Effector

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

scholarly journals Immune cells as targets for cardioprotection: new players and novel therapeutic opportunities

2019 ◽  
Vol 115 (7) ◽  
pp. 1117-1130 ◽  
Author(s):  
Ioanna Andreadou ◽  
Hector A Cabrera-Fuentes ◽  
Yvan Devaux ◽  
Nikolaos G Frangogiannis ◽  
Stefan Frantz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Inflammatory Reaction ◽  
Immune Cells ◽  
Cell Response ◽  
Immune Cell ◽  
Left Ventricular ◽  
Lymphoid Cells ◽  
Inflammatory Phase ◽  
Anti Inflammatory ◽  
Immune Cell Response

Abstract New therapies are required to reduce myocardial infarct (MI) size and prevent the onset of heart failure in patients presenting with acute myocardial infarction (AMI), one of the leading causes of death and disability globally. In this regard, the immune cell response to AMI, which comprises an initial pro-inflammatory reaction followed by an anti-inflammatory phase, contributes to final MI size and post-AMI remodelling [changes in left ventricular (LV) size and function]. The transition between these two phases is critical in this regard, with a persistent and severe pro-inflammatory reaction leading to adverse LV remodelling and increased propensity for developing heart failure. In this review article, we provide an overview of the immune cells involved in orchestrating the complex and dynamic inflammatory response to AMI—these include neutrophils, monocytes/macrophages, and emerging players such as dendritic cells, lymphocytes, pericardial lymphoid cells, endothelial cells, and cardiac fibroblasts. We discuss potential reasons for past failures of anti-inflammatory cardioprotective therapies, and highlight new treatment targets for modulating the immune cell response to AMI, as a potential therapeutic strategy to improve clinical outcomes in AMI patients. This article is part of a Cardiovascular Research Spotlight Issue entitled ‘Cardioprotection Beyond the Cardiomyocyte’, and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

scholarly journals Impact of systemic therapy on circulating leukocyte populations in patients with metastatic breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Maria Larsson ◽  
Anna Roxå ◽  
Karin Leandersson ◽  
Caroline Bergenfelz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Natural Killer ◽  
Endocrine Therapy ◽  
Immune Cells ◽  
Systemic Therapy ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Cell Populations

Abstract Tumors affect the immune system, locally and systemically. The frequencies of specific circulating immune cell populations correlate with disease progression as well as prognosis of the patients. Although largely neglected, conventional antitumoral therapies often possess immunomodulatory properties and affect the levels of specific immune cell populations. Most information, however, derive from animal or in vitro studies. As this could impact prognosis as well as response to therapy, further studies of the effects of treatment on circulating immune cells in patients are warranted. In this pilot study, we evaluated a wide panel of circulating immune cells over time (up to six months) in ten patients with metastatic breast cancer receiving standard antitumoral regimens. Overall, endocrine therapy tends to enrich for natural killer (NK) and natural killer T (NKT) cells in the circulation, whereas both chemotherapy and endocrine therapy reduce the levels of circulating monocytic myeloid-derived suppressor cells (Mo-MDSCs). This indicates that the systemic immunosuppressive profile observed in patients tends to revert over the course of systemic therapy and holds promise for future combination treatment with standard antitumoral agents and immunotherapy.

Anti-lactadherin antibodies in anti-angiogenic cancer therapy of breast cancer stem cells

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14138-14138 ◽  
Author(s):  
A. A. Epenetos ◽  
G. Bower ◽  
M. Deonarain ◽  
L. Bonney
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Human Breast Cancer ◽  
Tumor Vasculature ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Integrin Receptor ◽  
Receptor Signalling

14138 Background: Angiolix (Hu-Mc3) is a humanized monoclonal antibody that recognizes a migrating adhesion molecule called Lactadherin. This novel antibody has a high affinity for its antigen and recognizes an epitope on Lactadherin which interacts with the the ’RGD’- motif found on integrin receptors on newly formed endothelial cells. Lactadherin binding leads to signalling via a VEGF-independent integrin receptor signalling cascade leading to vascular endothelial cell profileration. Lactadherin binding may also increase the potency of VEGF-VEGF receptor signalling. Methods: We studied the expression of Lactadherin on breast cancer cell lines, the biodistribution of Angiolix in human breast cancer xeografts and its ability to inhibit tumor growth in vivo. Results: Our data show that tumor cells express lactadherin in vivo and that Angiolix could achieve more than 75% growth inhibition of human breast cancer growing as xenografts . Conclusions: In view of the recent finding that cancer stem cells can over-express the pro-angiogenic VEGF and make a major contribution to tumor vasculature proliferation leads to the possibility that Angiolix may be able to act to specifically target breast cancer stem cell and cause tumor regression by blocking the growth of tumor vasculature by its ability to neutralise Lactadherin-integrin receptor binding. [Table: see text]

scholarly journals Epigenetic Quantification of Circulating Immune Cells in Peripheral Blood of Triple-Negative Breast Cancer patients

2021 ◽  
Author(s):  
Mehdi Manoochehri ◽  
Thomas Hielscher ◽  
Nasim Borhani ◽  
Clarissa Gerhäuser ◽  
Olivia Fletcher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Triple Negative Breast Cancer ◽  
Immune Cells ◽  
Triple Negative ◽  
Immune Cell ◽  
Nk Cell ◽  
Cell Type ◽  
Cell Ratio ◽  
Immune Cell Type

Abstract Background: A shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC). Methods: Leukocyte subtype-specific un/methylated CpG sites were selected and methylation levels at these sites used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls. Results: The mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66-4.29), all Padj.<1e-04). A higher neutrophil ratio and lower ratios of NK cells, CD4+ T cells, CD8+ T cells, monocytes, and B cells were associated with TNBC. The strongest association was observed with decreased NK cell ratio (OR range (1.28-1.42), all Padj.<1e-04). The NK cell ratio was also significantly lower in pre-diagnostic samples of TNBC cases compared with controls (P=0.019).Conclusion: This immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention.

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