scholarly journals Mitotic quiescence in hepatic cancer stem cells: An incognito mode

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Kandasamy Ashokachakkaravarthy ◽  
Biju Pottakkat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Proliferating Cells ◽  
Recurrence Rates

Hepatocellular carcinoma represents one of the most aggressive cancers with high recurrence rates. The high recurrence is a major problem in the management of this disease. Cancer stem cells (CSCs) are often regarded as the basis of cancer recurrence. The anti-proliferative therapy kills the proliferating cells but induces mitotic quiescence in CSCs which remain as residual dormant CSCs. Later on, withdrawal of treatment reactivates the residual CSCs from dormancy to produce new cancer cells. The proliferation of these newly formed cancer cells initiates new tumor formation in the liver leading to tumor recurrence. HCC cells evade the immune surveillance via modulating the key immune cells by alpha feto-protein (AFP) secreted from CSCs or hepatic progenitor cells. This AFP mediated immune evasion assists in establishing new tumors by cancer cells in the liver. In this review, we will summarise the CSC mechanisms of recurrence, mitotic quiescence, dormancy and reactivation of CSCs, metastasis and immune evasion of hepatocellular carcinoma.

scholarly journals Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Undifferentiated Cancer

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.

scholarly journals PD-L1 Expression in Human Breast Cancer Stem Cells Is Epigenetically Regulated through Posttranslational Histone Modifications

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Pramod Darvin ◽  
Varun Sasidharan Nair ◽  
Eyad Elkord
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Line ◽  
Histone Modifications ◽  
Immune Evasion ◽  
Breast Cancer Cells ◽  
Posttranslational Histone Modifications ◽  
Mcf 7

Tumor progression through immune evasion is a major challenge in cancer therapy. Recent studies revealed that enhanced PD-L1 expression in cancer stem cells is linked to immune evasion. Understanding the mechanisms behind this PD-L1 overexpression in cancer stem cells is critical for developing more effective strategies for preventing immune evasion and increasing the efficacy of anti-PD-1/PD-L1 therapy. Tumorsphere formation in breast cancer cells enhanced epithelial to mesenchymal transition (EMT), which is evident by increased expression of mesenchymal markers. In this study, we analyzed CpG methylation of PD-L1 promoter in MCF-7 and BT-549 breast cancer cells and tumorspheres derived from them. PD-L1 promoter was significantly hypomethylated in MCF-7 tumorspheres, but not from BT-549 tumorspheres, compared with their cell line counterparts. The active demethylation of PD-L1 promoter was confirmed by the increase in the distribution of 5hmC and decrease in 5mC levels and the upregulation of TET3 and downregulation of DNMTs enzymes in MCF-7 tumorspheres, compared with the cell line. Additionally, we checked the distribution of repressive histones H3K9me3, H3K27me3, and active histone H3K4me3 in the PD-L1 promoter. We found that distribution of repressive histones to the PD-L1 promoter was lower in tumorspheres, compared with cell lines. Moreover, an overexpression of histone acetylation enzymes was observed in tumorspheres suggesting the active involvement of histone modifications in EMT-induced PD-L1 expression. In summary, EMT-associated overexpression of PD-L1 was partially independent of promoter CpG methylation and more likely to be dependent on posttranslational histone modifications.

scholarly journals Tissue-specific cancer stem cells: reality or a mirage?

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Tarik Regad
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Cancer Recurrence ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Significant Progress ◽  
Specific Cancer

<em>Equo ne credite, Teucri. Quidquid id est, timeo Danaos et dona ferentes</em> (<em>Do not trust the horse, Trojans! Whatever it is, I fear the Greeks, even bringing gifts</em>) said Laocoön (Virgil, the <em>Aeneid book</em>). Cancer stem cells (CSCs) are populations of cancer cells that can be found in different cancerous tissues and organs, and have properties that are similar to normal stem cells. They are thought to be chemo-resistant and radioresistant and are therefore responsible for cancer recurrence and relapse encountered in cancer patients following chemotherapy and radiotherapy. Although significant progress has been made to characterise CSCs, it is becoming clear that the failure of cancer therapies directed against certain types of aggressive cancers is due to the presence of these malignant cells. Cancer therapies that will rely on a combination of CSCs-targeted therapies, chemotherapy and radiotherapy are more likely to succeed in eradicating aggressive cancers and prevent recurrence in treated patients.

scholarly journals Propofol Reduced Mammosphere Formation of Breast Cancer Stem Cells via PD-L1/Nanog In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaobei Zhang ◽  
Fangxuan Li ◽  
Ying Zheng ◽  
Xiaokun Wang ◽  
Kaiyuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Breast Cancer Stem Cells ◽  
Mammosphere Formation ◽  
Significant Difference

Several researches revealed that propofol, a hypnotic intravenous anesthesia agent, could inhibit the cancer cell proliferation and tumor formation, which might affect cancer recurrence or metastasis and impact patients’ prognosis. Cancer stem cells (CSCs) comprised a tiny fraction of tumor bulk and played a vital role in cancer recurrence and eventual mortality. This study investigates the effect of propofol on breast cancer stem cells (BCSCs) in vitro and the underlying molecular mechanisms. Tumor formation of CSCs was measured by mammosphere culture. Cultured BCSCs were exposed to different concentrations and durations of propofol. Cell proliferation and self-renewal capacity were determined by MTT assays. Expressions of PD-L1 and Nanog were measured using western blotting and real-time PCR. We knocked down the PD-L1 expression in MDA-MB-231 cells by lentivirus-mediated RNAi technique, and the mammosphere-forming ability of shControl and shPD-L1 under propofol treatment was examined. Mammosphere culture could enrich BCSCs. Compared with control, cells exposed to propofol for 24 h induced a larger number of mammosphere cells (P=0.0072). Levels of PD-L1 and Nanog were downregulated by propofol. Compared with shControl stem cells, there was no significant difference in the inhibitory effect of propofol on the mammosphere-forming ability of shPD-L1 stem cells which indicated that the inhibition of propofol could disappear in PD-L1 knockdown breast stem cells. Propofol could reduce the mammosphere-forming ability of BCSCs in vitro. Mechanism experiments indicated that the inhibition of propofol in mammosphere formation of BCSCs might be mediated through PD-L1, which was important to maintain Nanog.

scholarly journals Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1896 ◽  
Author(s):  
Kevin Dzobo ◽  
Dimakatso Alice Senthebane ◽  
Chelene Ganz ◽  
Nicholas Ekow Thomford ◽  
Ambroise Wonkam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Treatment Strategies ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Microenvironmental Factors ◽  
Novel Treatment Strategies

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

scholarly journals Targeting Metabolism to Induce Cell Death in Cancer Cells and Cancer Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claire Pecqueur ◽  
Lisa Oliver ◽  
Kristell Oizel ◽  
Lisenn Lalier ◽  
François M. Vallette
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Tumor Formation ◽  
Successful Therapy ◽  
Mechanisms Of Resistance ◽  
Induce Cell Death ◽  
Abnormal Metabolism ◽  
Key Drivers

Abnormal metabolism and the evasion of apoptosis are considered hallmarks of cancers. Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes.

scholarly journals Natural Compounds Targeting Cancer Stem Cells: A Promising Resource for Chemotherapy

2019 ◽  
Vol 19 (15) ◽  
pp. 1796-1808 ◽  
Author(s):  
Plabon K. Das ◽  
Tasnim Zahan ◽  
Md. Abdur Rakib ◽  
Jahan A. Khanam ◽  
Suja Pillai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Natural Compounds ◽  
Biologically Active ◽  
Cancer Pathogenesis ◽  
Distant Organ

Background:Cancer Stem Cells (CSCs) are the subpopulation of cancer cells which are directly involved in drug resistance, metastases to distant organ and cancer recurrence.Methods:A systematic literature search was conducted through various electronic databases including, Pubmed, Scopus, Google scholar using the keywords "cancer stem cells" and "natural compounds" in the present study. Articles published between 1999 and 2019 were reviewed. All the expositions concerning CSCs associated cancer pathogenesis and therapy resistance, as well as targeting these properties of CSCs by natural compounds were selected for the current study.Results:Natural compounds have always been thought as a rich source of biologically active principles, which target aberrantly activated signaling pathways and other modalities of CSCs, while tethering painful side effects commonly involved in the first-line and second-line chemo-radiotherapies. In this review, we have described the key signaling pathways activated in CSCs to maintain their survival and highlighted how natural compounds interrupt these signaling pathways to minimize therapy resistance, pathogenesis and cancer recurrence properties of CSCs, thereby providing useful strategies to treat cancer or aid in cancer therapy improvement. Like normal stem cells, CSCs rely on different signaling pathways and other properties for their maintenance. Therefore, the success of cancer treatment depends on the development of proper anti-neoplastic drugs capable of intercepting those signaling pathways as well as other properties of CSCs in order to eradicate this evasive subpopulation of cancer cells.Conclusion:Compounds of natural origin might act as an outstanding source to design novel therapies against cancer stem cells.

scholarly journals Redox Regulation in Cancer Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shijie Ding ◽  
Chunbao Li ◽  
Ninghui Cheng ◽  
Xiaojiang Cui ◽  
Xinglian Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Redox Regulation ◽  
Cancer Recurrence ◽  
Ros Generation ◽  
Self Renewal ◽  
Cellular Processes

Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.

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