scholarly journals Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Guang Zhang ◽  
Zhongxia Wang ◽  
Weihuan Luo ◽  
Hongbo Jiao ◽  
Junhua Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Expression Level ◽  
Stem Cell Marker ◽  
Migration And Invasion ◽  
Close Relationship ◽  
A Minor

Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC) remains disastrous. Cancer stem cells (CSCs) may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2) is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors.Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro.Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors.Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

Tropism of liver epithelial cells toward hepatocellular carcinoma in vitro and in vivo with altering gene expression of cancer stem cells

2018 ◽  
Vol 215 (4) ◽  
pp. 735-743
Author(s):  
Kuo-Shyang Jeng ◽  
Chi-Juei Jeng ◽  
Wen-Juei Jeng ◽  
I-Shyan Sheen ◽  
Shih-Yun Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Epithelial Cells ◽  
Cancer Stem Cells ◽  
Liver Epithelial Cells

scholarly journals Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 79 ◽  
Author(s):  
Noothan Jyothi Satheesh ◽  
Samson Mathews Samuel ◽  
Dietrich Büsselberg
Keyword(s):  
Stem Cells ◽  
Cancer Research ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Vitamin C ◽  
Resistance Mechanism ◽  
Immune Defense ◽  
The Body ◽  
Treatment Modalities ◽  
Migration And Invasion

Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.

Computational modeling reveals MAP3K8 as mediator of resistance to vemurafenib in thyroid cancer stem cells

2018 ◽  
Vol 35 (13) ◽  
pp. 2267-2275 ◽  
Author(s):  
Fiorenza Gianì ◽  
Giulia Russo ◽  
Marzio Pennisi ◽  
Laura Sciacca ◽  
Francesco Frasca ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Thyroid Cancer ◽  
Cancer Stem Cells ◽  
Braf Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Braf V600e ◽  
Supplementary Information

Abstract Motivation Val600Glu (V600E) mutation is the most common BRAF mutation detected in thyroid cancer. Hence, recent research efforts have been performed trying to explore several inhibitors of the V600E mutation-containing BRAF kinase as potential therapeutic options in thyroid cancer refractory to standard interventions. Among them, vemurafenib is a selective BRAF inhibitor approved by Food and Drug Administration for clinical practice. Unfortunately, vemurafenib often displays limited efficacy in poorly differentiated and anaplastic thyroid carcinomas probably because of intrinsic and/or acquired resistance mechanisms. In this view, cancer stem cells (CSCs) may represent a possible mechanism of resistance to vemurafenib, due to their self-renewal and chemo resistance properties. Results We present a computational framework to suggest new potential targets to overcome drug resistance. It has been validated with an in vitro model based upon a spheroid-forming method able to isolate thyroid CSCs that may mimic resistance to vemurafenib. Indeed, vemurafenib did not inhibit cell proliferation of BRAF V600E thyroid CSCs, but rather stimulated cell proliferation along with a paradoxical over-activation of ERK and AKT pathways. The computational model identified a fundamental role of mitogen-activated protein kinase 8 (MAP3K8), a serine/threonine kinase expressed in thyroid CSCs, in mediating this drug resistance. To confirm model prediction, we set a suitable in vitro experiment revealing that the treatment with MAP3K8 inhibitor restored the effect of vemurafenib in terms of both DNA fragmentation and poly (ADP-ribose) polymerase cleavage (apoptosis) in thyroid CSCs. Moreover, MAP3K8 expression levels may be a useful marker to predict the response to vemurafenib. Availability and implementation The model is available in GitHub repository visiting the following URL: https://github.com/francescopappalardo/MAP3K8-Thyroid-Spheres-V-3.0. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals FTY720 Inhibits Expansion of Breast Cancer Stem Cells via PP2A Activation

2021 ◽  
Vol 22 (14) ◽  
pp. 7259
Author(s):  
Naoya Hirata ◽  
Shigeru Yamada ◽  
Shota Yanagida ◽  
Atsushi Ono ◽  
Yasunari Kanda
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Drug Repositioning ◽  
Immunosuppressive Agent ◽  
Stem Cell Markers ◽  
Breast Cscs ◽  
Therapeutic Drugs ◽  
A Minor

Growing evidence suggests that breast cancer originates from a minor population of cancer cells termed cancer stem cells (CSCs), which can be identified by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, novel therapeutic drugs for the eradication of CSCs have not been discovered yet. Recently, drug repositioning, which finds new medical uses from existing drugs, has been expected to facilitate drug discovery. We have previously reported that sphingosine kinase 1 (SphK1) induced proliferation of breast CSCs. In the present study, we focused on the immunosuppressive agent FTY720 (also known as fingolimod or Gilenya), since FTY720 is known to be an inhibitor of SphK1.We found that FTY720 blocked both proliferation of ALDH-positive cells and formation of mammospheres. In addition, we showed that FTY720 reduced the expression of stem cell markers such as Oct3/4, Sox2 and Nanog via upregulation of protein phosphatase 2A (PP2A). These results suggest that FTY720 is an effective drug for breast CSCs in vitro.

scholarly journals Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

2010 ◽  
Vol 2 (3) ◽  
pp. 114 ◽  
Author(s):  
Caecilia HC Sukowati ◽  
Natalia Rosso ◽  
Lory S Crocè ◽  
Claudio Tiribelli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Targeted Therapies ◽  
Hepatic Cancer

scholarly journals The Efficacy of PI3Kγ and EGFR Inhibitors on the Suppression of the Characteristics of Cancer Stem Cells

2021 ◽  
Author(s):  
Yanning Xu ◽  
Said M. Afify ◽  
Juan Du ◽  
Bingbing Liu ◽  
Qing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Recurrence ◽  
Significant Inhibition ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Self Renewal ◽  
Egfr Signaling Pathway

Abstract Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3Kγ inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3Kγ, might be a promising therapeutic strategy against CSCs defeating cancer in the near future

scholarly journals LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis

2018 ◽  
Vol 48 (2) ◽  
pp. 540-555 ◽  
Author(s):  
Zhi-an Ling ◽  
Dan-dan Xiong ◽  
Rong-mei Meng ◽  
Jie-Mei Cen ◽  
Na Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kegg Pathway ◽  
Expression Level ◽  
Migration And Invasion ◽  
In Vitro Experiments ◽  
Ppi Network ◽  
Network Analyses ◽  
Qpcr Analysis ◽  
Lncrna Neat1

Background/Aims: Accumulated evidence indicates that lncRNA NEAT1 has important roles in various malignant tumors. In this study, we conducted a comprehensive analysis to explore the exact role of NEAT1 in hepatocellular carcinoma (HCC). Methods: The effects of NEAT1 on cell proliferation, apoptosis, migration, and invasion were measured by in vitro experiments. The expression level and clinical value of NEAT1 in HCC was evaluated based on data from The Cancer Genome Atlas (TCGA), Oncomine, and in-house real-time quantitative (RT-qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analyses were conducted to investigate the potential molecular mechanisms of NEAT1. Results: NEAT1 siRNA not only inhibited proliferation, migration, and invasion of HCC cells but also induced HCC cell apoptosis. A total of four records from TCGA, Oncomine, and RT-qPCR analysis were combined to assess the expression level of NEAT1 in HCC. The pooled standard mean deviation (SMD) indicated that NEAT1 was up-regulated in HCC (SMD = 0.54; 95% CI, 0.36–0.73; P < 0.0001). The area under the curve value of the summary receiver operating characteristic curve was 0.71. NEAT1 expression was also related to race (P = 0.025) and distant metastasis (P = 0.002). Additionally, the results of GO, KEGG pathway, and PPI network analyses suggest that NEAT1 may promote the progression of HCC by interacting with several tumor-related genes (SP1, MDM4, CREBBP, TRAF5, CASP8, TRAF1, KAT2A, and HIST4H4). Conclusions: NEAT1 contributes to the deterioration of HCC and provides a potential biomarker for the diagnosis and therapy of HCC.

scholarly journals Musashi2 contributes to the maintenance of CD44v6+ liver cancer stem cells via notch1 signaling pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Xiju Wang ◽  
Ronghua Wang ◽  
Shuya Bai ◽  
Si Xiong ◽  
Yawen Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Tissue Microarray ◽  
Migration And Invasion ◽  
Liver Cancer Stem Cells ◽  
Notch1 Signaling ◽  
And Function

Abstract Background Liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) development, metastasis, and drug resistance. MSI2 and Notch1 signaling are involved in the maintenance of CSCs. However, it is unknown whether MSI2 and Notch1 are involved in the maintenance of CD44v6+ LCSCs. Therefore, we investigated the clinical significance and function of MSI2 and its relationship with Notch1 signaling in the maintenance of stemness properties in CD44v6+ LCSCs. Methods The expression of MSI2 and CD44v6 were detected by fresh specimens and a HCC tissue microarray. The tissue microarray containing 82 HCC samples was used to analyze the correlation between CD44v6 and MSI2. CD44v6+/− cells were isolated using microbeads sorting. We explored the roles of MSI2 and Notch1 signaling in CD44v6+ LCSCs by sphere formation assay, transwell assay, clone formation assay in vitro, and xenograft tumor models in vivo. A Notch RT2 PCR Array, Co-immunoprecipitation, and RNA-immunoprecipitation were used to further investigate the molecular mechanism of MSI2 in activating Notch1 signaling. Results Here, we found MSI2 expression was positively correlated with high CD44v6 expression in HCC tissues, and further correlated with tumor differentiation. CD44v6+ cells isolated from HCC cell lines exhibited increased self-renewal, proliferation, migration and invasion, resistance to Sorafenib and tumorigenic capacity. Both MSI2 and Notch1 signaling were elevated in sorted CD44v6+ cells than CD44v6- cells and played essential roles in the maintenance of stemness of CD44v6+ LCSCs. Mechanically, MSI2 directly bound to Lunatic fringe (LFNG) mRNA and protein, resulting in Notch1 activation. Conclusions Our results demonstrated that MSI2 maintained the stemness of CD44v6+ LCSCs by activating Notch1 signaling through the interaction with LFNG, which could be a potential molecular target for stem cell-targeted therapy for liver cancer.

Sign in / Sign up

Export Citation Format

Share Document