scholarly journals ASSOCIATION OF CD44+CD24−/low WITH MARKERS OF AGGRESSIVENESS AND PLASTICITY OF CELL LINES AND TUMORS OF PATIENTS WITH BREAST CANCER

2017 ◽  
Vol 39 (3) ◽  
pp. 203-211 ◽  
Author(s):  
V F Chekhun ◽  
N Yu Lukianova ◽  
S V Chekhun ◽  
N O Bezdieniezhnykh ◽  
T V Zadvorniy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
High Expression ◽  
Immunohistochemical Method ◽  
Stem Cell Markers ◽  
Development Of Resistance ◽  
Grade Malignancy ◽  
Mcf 7

Aim: To search for additional molecular-biological markers of cancer stem cell (CSC) involved in the development of intra-tumor heterogeneity for the detection of features of the breast cancer (BC) pathogenesis. Materialts and Methods: Expression of estrogen receptors (ER), progesterone receptors (PR), Her2/neu, E- and N-cadherin, CD24, CD44, Bcl-2, Bax, Slug, P-gp, glutathioneS-transferase (GST) and metallothionein in cell lines was determined by the immunocytochemical method. Expression of ER, PR, Her2/neu, CD24 and CD44 in the surgical material of BC patients were determined by the immunohistochemical method. The levels of the miRNA were determined using real-time polymerase chain reaction. Results: Cells of high-grade malignancy (HGM), MDA-MB-231 and MDA-MB-468 are characterized by high expression of stem cell markers compared to the cells of low-grade malignancy (LGM), T47D and MCF-7: CD44 levels in T47D and MCF-7 cells were in range of 72–79 points, which is significantly lower than in HGM cells (p < 0.05). Also, HGM cells with the properties of CSC were characterized by high expression of antiapoptotic proteins, the transcription factor Slug, and low levels of proapoptotic protein Bax (p < 0.05) compared to LGM cells. In cells with CSC characteristics an increased expression of transferrin and its receptor, ferritin, fentorin and hepcidin was revealed indicating activation of the endogenous iron metabolism. The characteristic feature of HGM cells with CSC phenotype were the increased levels of oncogenic miR-221, -155 and -10b by 60%, 92% and 78%, respectively, and decreased levels of oncosuppressive miR-29b, -34a and -200b by 8.4 ± 0.3, 4.6 ± 0.2, and 3.4 ± 0.6 times compared to MCF-7 line cells. It has been established that the development of resistance to cytostatics is accompanied by increased aggressiveness of tumor cells, loss of expression of hormonal receptors and acquiring of stem phenotype. In particular, increased expression of P-gp was observed in BC cells during the development of resistance to doxorubicin, of GST during the development of resistance to cisplatin along with increased CD44 expression (p < 0.05). We have revealed the relation between the presence of cells with the CSC phenotype (CD44+CD24-/low) and clinical and pathological characteristics of BC patients, their survival and BC sensitivity to neoadjuvant therapy (p > 0.05). Conclusions: The dependence between the expression of CSC markers and the degree of malignancy of tumor cells, development of resistance to cytostatics in vitro was established as well as the predictive value of the detection of the CSC for the individual prognosis of the BC course and sensitivity of the tumors to the treatment.

scholarly journals Identification of Novel Cancer Stem Cell Markers in Glioblastoma by Comparing Tumor Cells with Stem-cell-like Cell Lines

2021 ◽  
Vol 11 (2) ◽  
pp. 1567-1583
Author(s):  
Divya G.
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Microarray Dataset ◽  
Gene Expression Omnibus ◽  
Stem Cell Markers ◽  
Cancer Stem Cell Markers

Aim. The aim of this study is to identify differential gene expression for glioblastoma tumor cells, normoxic and hypoxic glioblastoma stem-like cell lines. Finding the upregulated and downregulated gene and pathway interactions. Analysis to find the differential expression genes and pathway interactions. Materials and methods. The gene expression profiling data from the microarray dataset GSE45117 from the Gene Expression Omnibus (GEO) database, as well as differentially expressed genes (DEGs) between the 2 categories, are used in this analysis. 4 Samples of Glioblastoma tumors were considered as group 1 and 4 samples of normoxic and Hypoxic glioblastoma stem-like cell lines were considered as group 2 in the GEO2R web tool that has been used to screen them. Results. The gene-gene interactions among the DEGs and the GGI network with 37 nodes and 13 edges. The stem-cell-like cell lines showed lower expression of endothelin-related genes such as EDN3 and EDNRA along with dysregulation of enzymes such as PDK1, PGK1 which points to dysregulation of cellular respiratory pathways. This effect in consensus with under expression of cell attachment genes such as COL2A1, COL5A2, COL15A1 denotes a strong shift toward metastasis. Conclusion. Thus, a computational pipeline for identifying the significant genes and pathways involved in the glioblastoma tumors and glioblastoma stem-like cell lines. This study provides a path towards discovering potential leads for the treatment of glioblastoma and aids in comprehending the underlying novel molecular mechanisms.

scholarly journals Pentadecanoic Acid, an Odd-Chain Fatty Acid, Suppresses the Stemness of MCF-7/SC Human Breast Cancer Stem-Like Cells through JAK2/STAT3 Signaling

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1663
Author(s):  
Ngoc Bao To ◽  
Yen Thi-Kim Nguyen ◽  
Jeong Yong Moon ◽  
Meran Keshawa Ediriweera ◽  
Somi Kim Cho
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Saturated Fatty Acids ◽  
Stem Cell Markers ◽  
Pentadecanoic Acid ◽  
Human Breast ◽  
Stat3 Signaling ◽  
Mcf 7

Saturated fatty acids possess few health benefits compared to unsaturated fatty acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated fatty acids in human health. In this study, the anti-cancer effects of pentadecanoic acid were evaluated in human breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem cell properties compared to the parental MCF-7 cells. Pentadecanoic acid exerted selective cytotoxic effects in MCF-7/SC compared to in the parental cells. Moreover, pentadecanoic acid reduced the stemness of MCF-7/SC and suppressed the migratory and invasive ability of MCF-7/SC as evidenced by the results of flow cytometry, a mammosphere formation assay, an aldehyde dehydrogenase activity assay, and Western blot experiments conducted to analyze the expression of cancer stem cell markers—CD44, β-catenin, MDR1, and MRP1—and epithelial–mesenchymal transition (EMT) markers—snail, slug, MMP9, and MMP2. In addition, pentadecanoic acid suppressed interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cell cycle arrest at the sub-G1 phase, and promoted caspase-dependent apoptosis in MCF-7/SC. These findings indicate that pentadecanoic acid can serve as a novel JAK2/STAT3 signaling inhibitor in breast cancer cells and suggest the beneficial effects of pentadecanoic acid-rich food intake during breast cancer treatments.

scholarly journals Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Natalia Krawczyk ◽  
Franziska Meier-Stiegen ◽  
Malgorzata Banys ◽  
Hans Neubauer ◽  
Eugen Ruckhaeberle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Current Data ◽  
Stem Cell Markers ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulation. During EMT epithelial antigens are downregulated; thus, such tumor cells might elude classical epithelial marker-based detection. Several researchers postulated that some CTCs express stem cell-like phenotype; this might lead to chemoresistance and enhanced metastatic potential of such cells. In the present review, we discuss current data on EMT and stem cell markers in CTCs of breast cancer and their clinical significance.

scholarly journals Kaempferol and docetaxel diminish side population and down-regulate some cancer stem cell markers in breast cancer cell line MCF-7

BIOCELL ◽  
2017 ◽  
Vol 41 (2) ◽  
pp. 33-40 ◽  
Author(s):  
SARA SOLTANIAN ◽  
HELIA RIAHIRAD ◽  
ATHAREH PABARJA ◽  
MOHAMMAD REZA KARIMZADEH ◽  
KOLSOUM SAEIDI
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
Side Population ◽  
Cancer Cell Line ◽  
Stem Cell Markers ◽  
Cancer Stem Cell Markers ◽  
Mcf 7

scholarly journals Interaction of Tumor Cells with the Hematopoietic Stem and Progenitor Cell Niche

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5139-5139 ◽  
Author(s):  
Abhishek Dhawan ◽  
Jens Friedrichs ◽  
Laura Bray ◽  
Lorenz C. Hofbauer ◽  
Manja Wobus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction The bone marrow microenvironment regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs), through a network dependent on cell-cell interaction. This interaction is mediated by morphogens, the extracellular matrix and cell adhesion molecules expressed and secreted by various cell types in the HSPC niche. Mesenchymal stromal cells (MSCs), as the major cellular component, maintain the stemness properties of the niche. The microenvironment thus becomes conducive for HSPCs to remain quiescent, thereby enabling long term self-renewal. Therefore, the safe haven in the bone marrow microenvironment and its constituent cell types can be targeted during tumorigenesis, thus making the niche neoplastic. Dissemination of breast cancer cells into the bone marrow has been described even in the early stages of the disease. The present study focuses on the influence of breast carcinomas on the genetic and functional profile of mesenchymal and hematopoietic progenitor cells of the bone marrow niche. Methods In vitro coculture models of breast cancer cell lines- MDA-MB231, MCF-7 and primary MSCs derived from the bone marrow of healthy donors were used in the study. Atomic- force microscopy based single-cell force spectroscopy (AFM-SCFS) and fluorescence based assays were used for cell adhesion experiments. Hydrogel based culture systems were used for 3-dimensional cocultures of breast cancer cells and MSCs. Hypoxic and normoxic culture conditions (0.5% and 20% oxygen respectively) were used for the experiments. Results The breast cancer cell lines caused a significant reduction in HSPC adhesion to MSCs (88% by MDA-MB 231 cells; p<0.005 and 73% by MCF-7 cells; p<0.005). AFM-SCFS studies also indicated a higher binding force between breast cancer cells and MSCs, as compared to HSPCs (MDA-MB231 cells-0.13nN, MCF-7 cells-0.074nN and HSPCs-0.05nN). MDA-MB231and MCF-7 cells express Intercellular adhesion molecule-1(ICAM-1), which has been shown to promote breast cancer metastasis (Hanlon et al, 2002; Rosette et al, 2005; Schröder C. et al, 2011). There was a significant difference in reduction of HSPC adhesion towards MSCs by ICAM-1 knockdown (ICAM-1 KD) tumor cells as compared to MDA-MB231 cells (84.83% by MDA-MB231 cells versus 28.11% by ICAM-1KD tumor cells, p<0.001). AFM-SCFS studies also showed a reduced binding force between ICAM-1 KD tumor cells and MSCs as compared to MDA-MB231cells (MDA-MB231 cells-0.14nN versus ICAM-1-KD tumor cells-0.05nN, p value<0.001). ICAM-1 KD studies thus showed that reduction in HSPC adhesion to MSCs by breast cancer cells was mediated through ICAM-1 signaling. A cytokine array was performed to investigate if breast cancer cell lines affect the cytokine profile of MSCs. The array showed altered expression of growth factors- Basic fibroblast growth factor (bFGF) and Platelet derived growth factor–beta (PDGF-BB) (2.2 fold upregulation and 0.5 fold downregulation in breast cancer cells- MSC cocultures respectively). Based on the array, a bFGF-mediated increase in the proliferation of MSCs and breast cancer cells in coculture was observed. The bFGF upregulation also caused an increased migration of MDA-MB231 cells towards MSCs in a transwell migration assay. An upregulation in the phosphorylation status of Akt was observed in breast cancer cells – MSC cocultures, as a downstream effect of upregulated bFGF levels. The bFGF-mediated increase in the proliferation of breast cancer cells and MSCs in coculture was shown to be dependent on the activation of PI3K-Akt pathway. The bFGF- mediated increase in the migration of MDA-MB231 cells towards MSCs was also inhibited upon addition of the PI3K blocker. Interestingly, the breast cancer cells caused a reduction in osteoblastic differentiation of MSCs by downregulation of PDGF-BB. Studies with 3-dimensional cocultures of breast cancer cells and MSCs also showed a reduction in osteoblastic differentiation of MSCs. Furthermore, long-term cocultures of breast cancer cells, HSPCs and MSCs showed reduced support for primitive HSPCs in the neoplastic niche. Conclusions These findings indicate a perturbed HSPC niche upon tumor invasion. The possible role of altered cytokine expression, consecutive downstream signaling in niche activation and bone turnover will be further studied using in vitro and in vivo approaches to recapitulate tumor micrometastases to the HSPC niche. Disclosures No relevant conflicts of interest to declare.

scholarly journals Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

2012 ◽  
Vol 81A (12) ◽  
pp. 1084-1091 ◽  
Author(s):  
A. R. M. Lobba ◽  
M. F. Forni ◽  
A. C. O Carreira ◽  
M. C. Sogayar
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Differential Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Malignant Breast
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