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 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 Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kung-Chao Chang ◽  
Ruo-Yu Chen ◽  
Yu-Chu Wang ◽  
Liang-Yi Hung ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tumor Formation ◽  
Stem Cell Markers ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractDiffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.

Pancreatic Carcinoma Cell Lines Reflect Frequency and Variability of Cancer Stem Cell Markers in Clinical Tissue

2012 ◽  
Vol 49 (2) ◽  
pp. 88-98 ◽  
Author(s):  
S. Bünger ◽  
M. Barow ◽  
C. Thorns ◽  
S. Freitag-Wolf ◽  
S. Danner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Pancreatic Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Cancer Stem Cell Markers ◽  
Carcinoma Cell Lines

scholarly journals Patient-derived cell lines and orthotopic mouse model of peritoneal carcinomatosis recapitulate molecular and phenotypic features of human gastric adenocarcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Shumei Song ◽  
Yan Xu ◽  
Longfei Huo ◽  
Shuangtao Zhao ◽  
Ruiping Wang ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Gastric Adenocarcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Stem Cell Markers ◽  
Orthotopic Mouse Model ◽  
Cancer Stem Cell Markers ◽  
Phenotypic Features

Abstract Background Gastric adenocarcinoma with peritoneal carcinomatosis (PC) is therapy resistant and leads to poor survival. To study PC in depth, there is an urgent need to develop representative PC-derived cell lines and metastatic models to study molecular mechanisms of PC and for preclinical screening of new therapies. Methods PC cell lines were developed from patient-derived PC cells. The tumorigenicity and metastatic potential were investigated by subcutaneously (PDXs) and orthotopically. Karyotyping, whole-exome sequencing, RNA-sequencing, and functional studies were performed to molecularly define the cell lines and compare genomic and phenotypic features of PDX and donor PC cells. Results We established three PC cell lines (GA0518, GA0804, and GA0825) and characterized them in vitro. The doubling times were 22, 39, and 37 h for GA0518, GA0804, and GA0825, respectively. Expression of cancer stem cell markers (CD44, ALDH1, CD133 and YAP1) and activation of oncogenes varied among the cell lines. All three PC cell lines formed PDXs. Interestingly, all three PC cell lines formed tumors in the patient derived orthotopic (PDO) model and GA0518 cell line consistently produced PC in mice. Moreover, PDXs recapitulated transcriptomic and phenotypic features of the donor PC cells. Finally, these cell lines were suitable for preclinical testing of chemotherapy and target agents in vitro and in vivo. Conclusion We successfully established three patient-derived PC cell lines and an improved PDO model with high incidence of PC associated with malignant ascites. Thus, these cell lines and metastatic PDO model represent excellent resources for exploring metastatic mechanisms of PC in depth and for target drug screening and validation by interrogating GAC for translational studies.

scholarly journals MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

2021 ◽  
Vol 22 (19) ◽  
pp. 10403
Author(s):  
Yuchuan Zhou ◽  
Hongxia Liu ◽  
Wang Zheng ◽  
Qianping Chen ◽  
Songling Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Method ◽  
Gene Expression Omnibus ◽  
Primary Brain Tumor ◽  
Study Gene Expression ◽  
Radiation Induced ◽  
Human Gbm

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment method of GBM. However, the intrinsic radioresistance of GBM cells is a key reason of poor therapeutic efficiency. Recently, many studies have shown that using the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in radiotherapy may improve the prognosis of GBM patients, but the underlying molecular mechanisms remain unclear. In this study, Gene Expression Omnibus (GEO) datasets GSE153982 and GSE131956 were analyzed to evaluate radiation-induced changes of gene expression in GBM without or with SAHA treatment, respectively. Additionally, the survival-associated genes of GBM patients were screened using the Chinese Glioma Genome Atlas (CGGA) database. Taking the intersection of these three datasets, 11 survival-associated genes were discovered to be activated by irradiation and regulated by SAHA. The expressions of these genes were further verified in human GBM cell lines U251, T98G, and U251 homologous radioresistant cells (U251R) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). It was found that MMP14 mRNA was considerably highly expressed in the radioresistant cell lines and was reduced by SAHA treatment. Transfection of MMP14 siRNA (siMMP14) suppressed cell survivals of these GBM cells after irradiation. Taken together, our results reveal for the first time that the MMP14 gene contributed to SAHA-induced radiosensitization of GBM.

Indirect Immunofluorescence and Tumorspheres Enrichment Technique for Identifying Cancer Stem Cell Markers in Cancer Cell Lines From Primary Oral Cancer Tissues: An In Vitro Study

2020 ◽  
Vol 11 (2) ◽  
pp. 224-230
Author(s):  
Vijay M. Kumbar ◽  
Uday M. Muddapur ◽  
Kishore G. Bhat ◽  
Shwetha H.R. ◽  
Manohar S. Kugaji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Lines ◽  
Indirect Immunofluorescence ◽  
In Vitro Study ◽  
Vitro Study ◽  
Stem Cell Markers ◽  
Rt Pcr ◽  
Cell Markers

Aim: The cancer stem cells (CSCs) are known to be responsible for drug resistance and cancer relapse in the treatment of cancer. Identification and isolation of CSCs and study of their properties will play a crucial role in developing an effective drug against these targets. The aim of the study was to isolate CSCs from primary cancer by the tumorspheres enrichment method, to confirm by indirect immunofluorescence and gene expression of stem cell markers by using real-time polymerase chain reaction (RT-PCR) technique. Materials and Methods: In this in vitro study, we enriched oral CSCs through tumorsphere formation assay from seven primary cultures of OSCC patients with defined serum media. The expression and localization of the cell surface markers of CD133 and CD44 were tested by indirect immunofluorescence. Gene expression of stem cell markers such as CD44, CD133, Oct4, Sox2, and Nanog were quantified by RT-PCR technique. One-way analysis of variance was applied to analyze gene expression. Results: Tumorsphere formation has been used to isolate the CSCs from the OSCC tissue culture. Both CD133 and CD44 antibody confirmed the presence of CSCs through indirect immunofluorescence. In comparison to parental cell lines, the expression levels of CD133, CD44, Oct4, Sox2, and Nanog stem cell were significantly higher in CSC-enriched subpopulations. Conclusions: The cost-effective spheroid enrichment and the indirect immunofluorescence methods are useful for the isolation of CSCs from the primary tumor.

scholarly journals Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach

2021 ◽  
Author(s):  
Zakieh Ghorbani ◽  
Mansour Heidari ◽  
Mojtaba Jafarinia ◽  
Mahdi Rohani ◽  
Abolfazl Akbari
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Photodynamic Therapy ◽  
Stem Cell Markers ◽  
Control Gene ◽  
Therapeutic Approaches ◽  
Cancer Stem Cell Markers ◽  
Control Gene Expression

Abstract Background: Cancer stem cells (CSC) play a crucial role in tumorigenesis, recurrence, metastasis, and chemoresistanc. Some studies suggest that hyperthermia and photodynamic therapy (PDT) may be effective for cancer treatment, particularly when combined with other therapeutic approaches. However, the results are conflicting. Our aim was to evaluate the effect of hyperthermia combined with PDT on colorectal CSC viability and the gene expression of the CSC markers.Results: Cell viability decrased by PDT (P=0.015) and the combination therapy (P=0.006) but not hyperthermia alone (P=0.4) compared to control. Gene expression of CSC markers significantly decreased in all therapies. Conclusion: Hyperthermia combined with PDT was more efficient in eliminating tumors than hyperthermia or PDT alone.

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