MicroRNA-194 inhibits PRC1 activation of the Wnt/β-catenin signaling pathway to prevent tumorigenesis by elevating self-renewal of non-side population cells and side population cells in esophageal cancer stem cells

2021 ◽  
Author(s):  
Shuang Cai ◽  
Yang Weng ◽  
Feng Miao
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Signaling Pathway ◽  
Side Population ◽  
Side Population Cells ◽  
Self Renewal

scholarly journals Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382098379
Author(s):  
Xiying Yu ◽  
Ying Teng ◽  
Xingran Jiang ◽  
Hui Yuan ◽  
Wei Jiang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Methylation Status ◽  
Methylation Profile ◽  
Cpg Dinucleotides ◽  
Genome Wide ◽  
Differentially Methylated Genes

Background: Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown. Methods: Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS). Results: Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways. Conclusions: When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.

Side population cells of pancreatic cancer show characteristics of cancer stem cells responsible for resistance and metastasis

2014 ◽  
Vol 10 (2) ◽  
pp. 215-227 ◽  
Author(s):  
Hanno Niess ◽  
Peter Camaj ◽  
Andrea Renner ◽  
Ivan Ischenko ◽  
Yue Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Side Population Cells

scholarly journals ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway

2020 ◽  
Vol 472 ◽  
pp. 70-80 ◽  
Author(s):  
Nuozhou Wang ◽  
Ming-yue Li ◽  
Yi Liu ◽  
Jianqing Yu ◽  
Jianwei Ren ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Self Renewal ◽  
Liver Cancer Stem Cells ◽  
Notch1 Signaling ◽  
Notch1 Signaling Pathway

Side Population Cells of Human B-Cell Non-Hodgkin Lymphoma Cell Lines May Contain Lymphoma-Stem Cells Responsible for Lymphoma Initiation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3105-3105
Author(s):  
Ha Yeon Lee ◽  
Mi Ran Lee ◽  
Won Seog Kim ◽  
Seok Jin Kim
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Side Population ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Side Population Cells ◽  
Hoechst 33342

Abstract Abstract 3105 Background: Cancer stem cells are considered to initiate cancer development, and such populations might be related with the resistance to treatment and relapse. There are accumulated data supporting the presence of cancer stem cells in several human cancers such as breast and colon cancers. In hematologic malignancy, the presence of cancer stem cells was supported by the previous studies from leukemia. However, there are few reports regarding the possibility of lymphoma stem cells. Side population cells are defined as cells that efficiently extrude the Hoechst 33342 dye, and hence remain negative for this fluorescent marker in flow cytometric analysis. The isolation of SP cells from total tumor cells has been used as a tool for cancer stem cell research. Methods: We performed the side-population analysis to isolate a stem-like cell population. The side population analysis was based on the modified Hoechst 33342 dye efflux assay. Thus, cells expressing ATP binding cassette (ABC) transporter subfamily G number 2 (ABCG2) on their surface efflux Hoechst 33342 dye. On the other hand, cells without ABCG2 expression cannot efflux dye. According to this different nature, we discriminated side population from non-side population. We isolated side population from three lymphoma cell lines, 1A2 (B-cell lymphoblastic lymphoma cell line), Raji (Burkitt lymphoma cell line), and Toledo (Diffuse large B-cell lymphoma cell line). We compared the SP cells with NSP cells from each cell line via in vitro propagation and colony forming assay. We also evaluated the ability of tumorigenesis in NOD/SCID mice and compared the gene expression via performing microarray. Results: We isolated a subset of cells (side population) from three cell lines. The number of side population was extremely small, so the ratio of SP to NSP was from 0.01% to 0.25% regardless of the type of lymphoma cell lines. The in vitro propagation for 3 weeks showed that the growth rate of the side population was significantly higher than non-side population in three cell lines. The life span of non-side population was limited while side population could continuously proliferate. Thus, non-side population could not be cultured over four weeks, and the proportion of viable cells was higher in the side population (≥95%) than non-side population (≤80%). The RT-PCR and confocal microscopy demonstrated the higher expression of ABCG2 in the side population compared to the non-side population. The inoculation of lymphoma cells (200 – 1000) into NOD/SCID mice showed the tumor formation in mice inoculated with side population cells while there was no tumor in non-side population. The hierarchical clustering of differentially expressed genes showed the different pattern of gene expression between side and non-side population in each cell line. Conclusion: This study suggests that the side population may contain a cell population highly capable of proliferation, and this population may have the characteristics of lymphoma stem-like cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Side population cells and liver cancer stem cells

2010 ◽  
Vol 18 (10) ◽  
pp. 971 ◽  
Author(s):  
Guang-Hui Qiang ◽  
De-Cai Yu ◽  
Chun-Ping Jiang
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Side Population ◽  
Side Population Cells ◽  
Liver Cancer Stem Cells

scholarly journals DNMT1 ablation suppresses tumorigenesis by inhibiting the self-renewal of esophageal cancer stem cells

Oncotarget ◽  
2018 ◽  
Vol 9 (27) ◽  
pp. 18896-18907 ◽  
Author(s):  
Ying Teng ◽  
Xiying Yu ◽  
Hui Yuan ◽  
Liping Guo ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
The Self ◽  
Self Renewal

Melanoma Stem Cells: The Dark Seed of Melanoma

2008 ◽  
Vol 26 (17) ◽  
pp. 2890-2894 ◽  
Author(s):  
Susan E. Zabierowski ◽  
Meenhard Herlyn
Keyword(s):  
Stem Cells ◽  
Side Population ◽  
Malignant Lesion ◽  
Therapeutic Strategies ◽  
Stem Cell Markers ◽  
Tumor Stem Cells ◽  
Side Population Cells ◽  
Self Renewal ◽  
Slow Cycling ◽  
Novel Therapeutic Strategies

Cells with stem-cell markers and features have recently been identified in melanoma tissues and cell lines. Melanoma stem-like cells possess many traits of tumor-initiating or tumor stem cells including self-renewal capacity, high tumorigenicity, and differentiation into various mesenchymal lineages, including melanocytic cells. Four subpopulations of melanoma-initiating cells have been distinguished: CD20+, CD133+, label-retaining or slow-cycling cells, and side-population cells with high efflux activities. Whether these are distinct or overlapping populations is currently under investigation. Ongoing studies are dissecting and characterizing the hierarchy of these subpopulations within a malignant lesion. Understanding these and the dynamics of clonal dominance will aid in the development of novel therapeutic strategies.

scholarly journals A2 KRT15+ TUMOR CELLS AS PUTATIVE CANCER STEM CELLS IN ESOPHAGEAL CANCER.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 2-3
Author(s):  
J Douchin ◽  
V Giroux
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Treatment Resistance ◽  
Esophageal Tumor ◽  
Basal Cells ◽  
Cell Of Origin ◽  
Self Renewal

Abstract Background Esophageal cancer is a particularly deadly cancer with a 5-year survival rate of only 14% in Canada. Treatment resistance ascribed for at least 30% of the death. The acquisition of resistance to radio- and chemotherapy is mostly attributed to the presence of cancer stem cells (CSCs) and their persistence following classical treatments. CSCs are a subpopulation of tumor cells with high self-renewal and multipotent capacity which amongst others contribute to tumor heterogeneity. Our previous work identified Krt15+ esophageal cells as a rare and long-lived subpopulation of basal cells with higher self-renewal and multipotent capacities than other basal cells. Furthermore, preliminary observations suggest that Krt15+ cells could act as the cell-of-origin for ESCC, the most prevalent type of esophageal cancer worldwide. Though, we still ignore the role of Krt15+ cells in later stages of esophageal cancer such as treatment resistance and if therefore, they could act as CSC. Aims Determine if Krt15+ cells act as CSCs in ESCC patients and if they could contribute to treatment resistance. Methods To do so, we used Krt15-CrePR1;R26mT/mG mice treated with the carcinogen 4 Nitroquinoline-1-oxide (4NQO) in their drinking water for 16 weeks to induce ESCC. Twelve weeks following the beginning of 4NQO treatment, we induced Cre recombination with RU486, a PR1 agonist, leading to GFP expression specifically in Krt15+ cells. Following 4NQO treatment, mice were put back on normal water for 8 to 12 weeks allowing tumors to grow. At euthanasia, esophageal tumor cells were FACS sorted to isolate Krt15+ (GFP+) and Krt15- (GFP-) cells, which were then grown as tumoroids. Results We first validated that 4NQO successfully induced the formation of esophageal lesions in our model, which comprises Krt15+ and Krt15- tumor cells. Tumoroids were then successfully derived from these FACS-sorted cell populations. We demonstrated the increase of CSC-like cells within Krt15+ tumoroids compared to Krt15- tumoroids by measuring the presence of CD44highCD24high cells, two well-known CSC markers, by flow cytometry. Interestingly, Krt15+ and Krt15- tumoroids are histologically distinct. As observed for normal cells, Krt15+ tumoroids appeared as more multipotent and heterogenous than Krt15- tumoroids. Furthermore, Krt15+ tumoroids display higher hyperplasia than Krt15- tumoroids suggesting that Krt15+ tumor cells are functionally distinct from Krt15- tumor cells. Conclusions Krt15+ tumoroids display higher CSC content and hyperplastic capacity suggesting their potential role in esophageal cancer. With this project, we aim to highlight the role of Krt15+ cells in treatment resistance and put forward new targets to overcome this deadly issue in ESCC patients. Funding Agencies CAGCanada research chair TIER 2

scholarly journals Therapeutic Strategies Against Cancer Stem Cells in Esophageal Carcinomas

2021 ◽  
Vol 10 ◽  
Author(s):  
Plabon Kumar Das ◽  
Farhadul Islam ◽  
Robert A. Smith ◽  
Alfred K. Lam
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Therapeutic Strategies ◽  
Self Renewal ◽  
Therapeutic Benefits ◽  
Esophageal Carcinomas

Cancer stem cells (CSCs) in esophageal cancer have a key role in tumor initiation, progression and therapy resistance. Novel therapeutic strategies to target CSCs are being tested, however, more in-depth research is necessary. Eradication of CSCs can result in successful therapeutic approaches against esophageal cancer. Recent evidence suggests that targeting signaling pathways, miRNA expression profiles and other properties of CSCs are important strategies for cancer therapy. Wnt/β-catenin, Notch, Hedgehog, Hippo and other pathways play crucial roles in proliferation, differentiation, and self-renewal of stem cells as well as of CSCs. All of these pathways have been implicated in the regulation of esophageal CSCs and are potential therapeutic targets. Interference with these pathways or their components using small molecules could have therapeutic benefits. Similarly, miRNAs are able to regulate gene expression in esophageal CSCs, so targeting self-renewal pathways with miRNA could be utilized to as a potential therapeutic option. Moreover, hypoxia plays critical roles in esophageal cancer metabolism, stem cell proliferation, maintaining aggressiveness and in regulating the metastatic potential of cancer cells, therefore, targeting hypoxia factors could also provide effective therapeutic modalities against esophageal CSCs. To conclude, additional study of CSCs in esophageal carcinoma could open promising therapeutic options in esophageal carcinomas by targeting hyper-activated signaling pathways, manipulating miRNA expression and hypoxia mechanisms in esophageal CSCs.

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