scholarly journals The role of cancer stem cells in glioblastoma

2014 ◽  
Vol 37 (6) ◽  
pp. E6 ◽  
Author(s):  
Swetha J. Sundar ◽  
Jason K. Hsieh ◽  
Sunil Manjila ◽  
Justin D. Lathia ◽  
Andrew Sloan
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Model ◽  
Critical Role ◽  
Treatment Resistance ◽  
Molecular Heterogeneity ◽  
Clinical Investigations ◽  
Stem Cell Model ◽  
Cancer Stem Cell Model

Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis. Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority. In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.

Invincible, but Not Invisible: Imaging Approaches Toward In Vivo Detection of Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2901-2910 ◽  
Author(s):  
Lori S. Hart ◽  
Wafik S. El-Deiry
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Natural Environment ◽  
Cell Model ◽  
Advanced Imaging ◽  
Stem Cell Model ◽  
Cancer Stem Cell Model

With evidence emerging in support of a cancer stem-cell model of carcinogenesis, it is of paramount importance to identify and image these elusive cells in their natural environment. The cancer stem-cell hypothesis has the potential to explain unresolved questions of tumorigenesis, tumor heterogeneity, chemotherapeutic and radiation resistance, and even the metastatic phenotype. Intravital imaging of cancer stem cells could be of great value for determining prognosis, as well as monitoring therapeutic efficacy and influencing therapeutic protocols. Cancer stem cells represent a rare population of cells, as low as 0.1% of cells within a human tumor, and the phenotype of isolated cancer stem cells is easily altered when placed under in vitro conditions. This represents a challenge in studying cancer stem cells without manipulation or extraction from their natural environment. Advanced imaging techniques allow for the in vivo observation of physiological events at cellular resolution. Cancer stem-cell studies must take advantage of such technology to promote a better understanding of the cancer stem-cell model in relation to tumor growth and metastasis, as well as to potentially improve on the principles by which cancers are treated. This review examines the opportunities for in vivo imaging of putative cancer stem cells with regard to currently accepted cancer stem-cell characteristics and advanced imaging technologies.

scholarly journals MicroRNA-28-5p Regulates Liver Cancer Stem Cell Expansion via IGF-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Qing Xia ◽  
Tao Han ◽  
Pinghua Yang ◽  
Ruoyu Wang ◽  
Hengyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Critical Role ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Background. MicroRNAs (miRNAs) play a critical role in the regulation of cancer stem cells (CSCs). However, the role of miRNAs in liver CSCs has not been fully elucidated. Methods. Real-time PCR was used to detect the expression of miR-miR-28-5p in liver cancer stem cells (CSCs). The impact of miR-28-5p on liver CSC expansion was investigated both in vivo and in vitro. The correlation between miR-28-5p expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results. Our data showed that miR-28-5p was downregulated in sorted EpCAM- and CD24-positive liver CSCs. Biofunctional investigations revealed that knockdown miR-28-5p promoted liver CSC self-renewal and tumorigenesis. Consistently, miR-28-5p overexpression inhibited liver CSC’s self-renewal and tumorigenesis. Mechanistically, we found that insulin-like growth factor-1 (IGF-1) was a direct target of miR-28-5p in liver CSCs, and the effects of miR-28-5p on liver CSC’s self-renewal and tumorigenesis were dependent on IGF-1. The correlation between miR-28-5p and IGF-1 was confirmed in human HCC tissues. Furthermore, the miR-28-5p knockdown HCC cells were more sensitive to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-28-5p may predict sorafenib benefits in HCC patients. Conclusion. Our findings revealed the crucial role of the miR-28-5p in liver CSC expansion and sorafenib response, rendering miR-28-5p an optimal therapeutic target for HCC.

scholarly journals The Contributions of Prostate Cancer Stem Cells in Prostate Cancer Initiation and Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 434 ◽  
Author(s):  
Wenjuan Mei ◽  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Yan Gu ◽  
Kuncheng Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Current Evidence ◽  
Target Cells ◽  
Mesenchymal Transition ◽  
Prostate Cancer Stem Cells

Research in the last decade has clearly revealed a critical role of prostate cancer stem cells (PCSCs) in prostate cancer (PC). Prostate stem cells (PSCs) reside in both basal and luminal layers, and are the target cells of oncogenic transformation, suggesting a role of PCSCs in PC initiation. Mutations in PTEN, TP53, and RB1 commonly occur in PC, particularly in metastasis and castration-resistant PC. The loss of PTEN together with Ras activation induces partial epithelial–mesenchymal transition (EMT), which is a major mechanism that confers plasticity to cancer stem cells (CSCs) and PCSCs, which contributes to metastasis. While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs. TP53 and RB1 suppress lineage plasticity through the inhibition of SOX2 expression. In this review, we will discuss the current evidence supporting a major role of PCSCs in PC initiation and metastasis, as well as the underlying mechanisms regulating PCSCs. These discussions will be developed along with the cancer stem cell (CSC) knowledge in other cancer types.

The critical role of SDF-1/CXCR4 axis in cancer and cancer stem cells metastasis

2008 ◽  
Vol 31 (9) ◽  
pp. 809-819 ◽  
Author(s):  
S. Gelmini ◽  
M. Mangoni ◽  
M. Serio ◽  
P. Romagnani ◽  
E. Lazzeri
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Critical Role ◽  
Cxcr4 Axis

scholarly journals Glioblastoma Multiformе Tumour Stem Cells as Potential Therapeutic Targets

2019 ◽  
Vol 9 (3) ◽  
pp. 216-222
Author(s):  
O. A. Beylerli ◽  
I. F. Gareev ◽  
Sh. Zhao ◽  
X. Chen
Keyword(s):  
Stem Cells ◽  
Critical Role ◽  
Molecular Heterogeneity ◽  
Immune Recognition ◽  
Malignant Tumours ◽  
Phenotypic Characteristics ◽  
Malignant Brain Tumours ◽  
First Time ◽  
Original Concept

The original concept of tumour stem cells (TSC) has been questioned ten years after TSCs in glioblastoma (GBM) had been described for the first time. Our understanding of cell heterogeneity in malignant brain tumours has become more complex. The improvements in our knowledge of tumour stem cells also impact on pre-clinical research and clinical practice. Chemoresistance is one of the key obstacles to success in treating malignant tumours; it results in tumour recurrence and metastatic spread. GBM relapse is almost universal, and its prognosis remains uncertain despite significant advances in treatment over the last decade. Tumour stem cells, glioblastoma stem cells (GSC) in particular, are highly resistant to chemotherapy, radiation therapy and immune recognition. GBM shows significant intratumoural phenotypic and molecular heterogeneity containing a population of tumour stem cells that contributes to the division of tumour cells supporting the resistance to treatment. TSCs are defined functionally by their ability for self-renewal and differentiation; they present a most diverse hierarchy of cells making up the tumour. The critical role of TSCs in glioblastoma pathogenesis makes the research into their molecular and phenotypic characteristics is a therapeutic priority.

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 Cancer Stem Cells-Role in Oral Squamous Carcinoma - A Review of Literature

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 153-158
Author(s):  
Deepthi Sogasu ◽  
Devaraj Ezhilarasan ◽  
Smiline Girija AS
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumour Size ◽  
Treatment Options ◽  
Cell Formation ◽  
Squamous Carcinoma ◽  
Treatment Resistance ◽  
Review Of Literature ◽  
Oral Squamous Carcinoma

The cancer stem cells (CSC) are responsible for the growth of cancerous tumours. The renewal of cancer stem cells is considered synonymous with that of normal cells. The cancer cells are considered a progeny of specific and designated stem cells. The identification of these cancer stem cells has proven to be more difficult than anticipated due to the specific niches they are present in, within the tumour. Oral squamous carcinoma is the Sixth most common cancer constituting up to 2–4% of all malignancies worldwide and with poor prognosis. Tumour size and extent of lymph node metastasis are the most important predictors. The CSC works on the mechanism of bulk tumour cell formation and treatment resistance. But there are increased studies under this topic as it has been found that specifically targeting these cells can curb cancer. This review compiles information about the role of CSC in oral squamous cell carcinomas, the applications of CSC, and their use in the development of novel treatment options for oral cancer.

scholarly journals The Crosstalk between Cancer Stem Cells and Microenvironment Is Critical for Solid Tumor Progression: The Significant Contribution of Extracellular Vesicles

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chiara Ciardiello ◽  
Alessandra Leone ◽  
Alfredo Budillon
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Progression ◽  
Cell Fate ◽  
Extracellular Vesicles ◽  
Significant Contribution ◽  
Critical Role ◽  
Mediated Communication

Several evidences nowadays demonstrated the critical role of the microenvironment in regulating cancer stem cells and their involvement in tumor progression. Extracellular vesicles (EVs) are considered as one of the most effective vehicles of information among cells. Accordingly, a number of studies led to the recognition of stem cell-associated EVs as new complexes able to contribute to cell fate determination of either normal or tumor cells. In this review, we aim to highlight an existing bidirectional role of EV-mediated communication—from cancer stem cells to microenvironment and also from microenvironment to cancer stem cells—in the most widespread solid cancers as prostate, breast, lung, and colon tumors.

scholarly journals The critical role of peroxiredoxin-2 in colon cancer stem cells

Aging ◽  
2021 ◽  
Author(s):  
Linglong Peng ◽  
Yongfu Xiong ◽  
Rong Wang ◽  
Ling Xiang ◽  
He Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Critical Role ◽  
Peroxiredoxin 2 ◽  
Colon Cancer Stem Cells
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