scholarly journals Stem Cells, Cancer and the Theory of Cancer Stem Cells in Solid Tumours

2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Abdulmajeed Almutary

Solid tumours are an immense cancer burden and a main therapeutic challenge. The theory of cancer stem cells provides an attractive cellular mechanism to account for the therapeutic resistance exhibited by many of these tumours. There is strong evidence that various solid tumours are hierarchically managed and sustained by notable subpopulations of cancer stem cells. Recent evidence of cancer stem cells emerged from a mouse model epithelial tumorigenesis, also some models of heterogeneity may apply. Haematopoietic stem cells (HSCs) have the capability to renew themselves and produce lineages of the blood; yet the signals that control HSc self-renewal remain indistinct. WnT signalling pathway has crucial role in the expression of activated p-catenin which expands the HSCs in a long-term cultures. In addition, Wnt signalling can interrupt the lymphocyte progenitor cells proliferation and affect the cells development. Other similar signalling pathways such as Notch and Hedgehog (Hh) are found in normal stem cells. Therapeutic targeting of cancer stem cells and tumour population could shed light on how to supress tumour growth. In this review, we suggest that by developing a new anti-cancer stem cell therapeutic agent that targets embryonic signalling pathways of cancer stem cells can improve the treatment of the disease

Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 138-138
Author(s):  
Keita Katsurahara ◽  
Atsushi Shiozaki ◽  
Michihiro Kudou ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
...  

Abstract Background Recent studies revealed that membrane proteins, such as ion transporters, are specifically activated in cancer stem cells (CSCs). Therefore, these molecules are receiving a great attention as new chemotherapeutic targets of malignant tumor. This study aimed to investigate the expression and activity of ion transport-related molecules in CSCs of esophageal squamous cell carcinoma (ESCC). Methods We sorted cells with high expression of ALDH1A1 via FACS, and then, CSCs were generated using the sphere formation assay. The gene expression profiles of CSCs were examined using a microarray analysis. Candidate genes of membrane proteins activated in CSCs were selected based on that microarray data. Anticancer effects induced by inhibition of the selected proteins were examined. Results ALDH1A1 mRNA and protein levels were certainly upregulated in CSCs compared with non-CSCs. Obtained CSCs were resistant to Cisplatin and had the ability of re-differentiation. The results of the microarray analysis revealed that expressions of 50 genes of plasma membrane proteins were changed in CSCs, and that several genes related to ion channels, including transient receptor potential cation channel subfamily V member 2 (TRPV2), were upregulated. The upregulation of TRPV2 mRNA were also validated in CSCs derived from two types of esophageal cancer cell lines using RT-PCR method. Tranilast, which is specific TRPV2 inhibitor, was more cytotoxic at lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Further, Tranilast significantly decreased the cell population with high ALDH1A1 expression in esophageal cancer cells. Conclusion The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and Tranilast, which is specific inhibitor of TRPV2, becomes a promising targeted therapeutic agent against ESCC. Disclosure All authors have declared no conflicts of interest.


BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Cristina Patru ◽  
Luciana Romao ◽  
Pascale Varlet ◽  
Laure Coulombel ◽  
Eric Raponi ◽  
...  

2019 ◽  
Vol 139 ◽  
pp. 298-313 ◽  
Author(s):  
Jan Skoda ◽  
Karolina Borankova ◽  
Patric J. Jansson ◽  
Michael L.-H. Huang ◽  
Renata Veselska ◽  
...  

2017 ◽  
Vol 18 (2) ◽  
pp. 156-174 ◽  
Author(s):  
Heron Torquato ◽  
Marcia Goettert ◽  
Giselle Justo ◽  
Edgar Paredes-Gamero

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 8 ◽  
Author(s):  
Xueqiao Jiao ◽  
Xianling Qian ◽  
Longyuan Wu ◽  
Bo Li ◽  
Yi Wang ◽  
...  

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.


2020 ◽  
Vol 10 ◽  
Author(s):  
Anna Mukha ◽  
Anna Dubrovska

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor‐regenerating and tumor‐propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.


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