Nanog, Cancer Stem Cells, and Resistance to Chemotherapy

2013 ◽  
Author(s):  
Hongmei Jiang
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Resistance To Chemotherapy

scholarly journals PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2168
Author(s):  
Balawant Kumar ◽  
Rizwan Ahmad ◽  
Swagat Sharma ◽  
Saiprasad Gowrikumar ◽  
Mark Primeaux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Therapy Resistance ◽  
Fluorescent Reporter ◽  
Combination Treatments ◽  
Gsk 3Β ◽  
Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

Determinants of resistance to chemotherapy and ionizing radiation in breast cancer stem cells

2016 ◽  
Vol 380 (2) ◽  
pp. 485-493 ◽  
Author(s):  
Athanasia Pavlopoulou ◽  
Yavuz Oktay ◽  
Konstantinos Vougas ◽  
Maria Louka ◽  
Constantinos E. Vorgias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ionizing Radiation ◽  
Breast Cancer Stem Cells ◽  
Resistance To Chemotherapy

scholarly journals Cancer Stem Cells and Targeting Strategies

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 926 ◽  
Author(s):  
Luisa Barbato ◽  
Marco Bocchetti ◽  
Anna Di Biase ◽  
Tarik Regad
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Survival Rates ◽  
Cancer Therapies ◽  
Cellular Processes ◽  
Cancer Initiation ◽  
Enzymatic Inactivation ◽  
Resistance To Chemotherapy ◽  
Made In

Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies.

scholarly journals Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jiangang Zhao ◽  
Jiahui Li ◽  
Hans A. Schlößer ◽  
Felix Popp ◽  
Marie Christine Popp ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Potential Role ◽  
Hematological Malignancies ◽  
Cancer Immunoediting ◽  
Therapeutic Implications ◽  
Novel Treatment ◽  
Cancer Initiation ◽  
Resistance To Chemotherapy

Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

Enzymatic tissue disintegration leads to the loss of immunophenotype of breast cancer stem cells.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13089-e13089
Author(s):  
Aleksandr B. Sagakyants ◽  
Anastasia O. Sitkovskaya ◽  
Tatiana V. Shamova ◽  
Svetlana Yu. Filippova ◽  
Elena S. Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Reference Sample ◽  
Enzyme Concentration ◽  
Isolated Cells ◽  
Prolonged Incubation ◽  
Viable Cells ◽  
Order Of Magnitude ◽  
Resistance To Chemotherapy

e13089 Background: Cancer stem cells (CSC) are a population in the complex hierarchy of tumor tissue responsible for growth, metastasis and resistance to chemotherapy and radiotherapy. The purpose of the study was to reveal the effect of the enzymatic disintegration of breast cancer (BC) tissue on the CSC immunophenotype. Methods: BC tumor samples obtained during surgery were placed for 2 hours in a sterile Hanks’ solution immediately after collection. Samples were fragmented to 1 mm in diameter, the fragments were evenly distributed into 4 Petri dishes with (6 cm diameter) and placed in DMEM medium (Gibco, USA) without collagenase and with the addition of collagenase (Biolot, Russia) to a final concentration of 150, 300 and 450 units/ml. Samples were cultured for 48 hours at 37°C and 5.5% CO2. On day 2, the samples incubated in collagenase were grinded by passing through tips of decreasing diameter; the reference sample was grinded in the Medimachine system (BD, USA). The effect of enzymatic tissue disintegration on the preservation of BC SC immunophenotype (CD24low/-CD44+) was evaluated using the BD FacsCanto II flow cytometer (BD, USA) and PE Mouse Anti-Human CD24 (clone ML5; BD, USA) and FITC Mouse Anti-Human CD44 (clone G44-26; BD, USA) antibodies. Results: The total number of isolated cells increased almost exponentially with increasing collagenase concentration. The trypan blue test showed that cell viability did not change significantly with an increase in collagenase concentration and was approximately 50%, being an order of magnitude higher compared to mechanical dissociation (4%). However, 48 h incubation in a collagenase solution led decreased the number of CD44+ cells in proportion to the enzyme concentration by 3 to 10 times in comparison with the control. Similarly, inhibition of CD24 expression was observed compared with the control, inevitably leading to a decreased purity of the isolated subpopulation with the CD24low/-CD44+ phenotype. Conclusions: Despite an increase in the yield of viable cells, prolonged incubation in a collagenase solution leads to a loss of the immunophenotype of BC SC.

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