scholarly journals Human ovarian cancer stem cells

Reproduction ◽  
2010 ◽  
Vol 140 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Sharmila A Bapat

The isolation and identification of stem-like cells in solid tumors or cancer stem cells (CSCs) have been exciting developments of the last decade, although these rare populations had been earlier identified in leukemia. CSC biology necessitates a detailed delineation of normal stem cell functioning and maintenance of homeostasis within the organ. Ovarian CSC biology has unfortunately not benefited from a pre-established knowledge of stem cell lineage demarcation and functioning in the normal organ. In the absence of such information, some of the classical parameters such as long-term culture-initiating assays to isolate stem cell clones from tumors, screening and evaluation of other epithelial stem cell surface markers, dye efflux, and label retention have been applied toward the putative isolation of CSCs from ovarian tumors. The present review presents an outline of the various approaches developed so far and the various perspectives revealed that are now required to be dealt with toward better disease management.

2018 ◽  
Author(s):  
Mary Youssef ◽  
Varsha S. Krish ◽  
Greer S. Kirshenbaum ◽  
Piray Atsak ◽  
Tamara J. Lass ◽  
...  

AbstractEnvironmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis.


2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Wenxiang Wang ◽  
Yuxia Gao ◽  
Jing Hai ◽  
Jing Yang ◽  
Shufeng Duan

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24− population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.


2014 ◽  
Vol 23 (7) ◽  
pp. 767-778 ◽  
Author(s):  
Anouk-Martine Teichert ◽  
Schreiber Pereira ◽  
Brenda Coles ◽  
Radha Chaddah ◽  
Susan Runciman ◽  
...  

2019 ◽  
Vol 21 (1) ◽  
pp. 45 ◽  
Author(s):  
Geoffrey Brown ◽  
Lucía Sánchez ◽  
Isidro Sánchez-García

Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These ‘hits’ do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (LMO2, associated with human acute T-lymphoblastic leukaemia) and BCR-ABLp210 (associated with human chronic myeloid leukaemia) oncogenes were active solely within the haematopoietic stem-cell compartment developed T-lymphocyte and neutrophil lineage-restricted leukaemia, respectively. This recapitulated the human form of these diseases. This ‘hardwiring’ of lineage affiliation, either throughout leukaemic stem cell development or at a particular stage, is different to the behaviour of normal haematopoietic stem cells. While normal cells directly commit to a developmental pathway, they also remain versatile and can develop into a terminally differentiated cell that is not part of the initial lineage. Many cancer stem cells do not have this versatility, and this is an essential difference between normal and cancer stem cells. In this report, we review findings that support this notion.


2014 ◽  
Vol 111 (48) ◽  
pp. 17266-17271 ◽  
Author(s):  
Suping Zhang ◽  
Bing Cui ◽  
Hsien Lai ◽  
Grace Liu ◽  
Emanuela M. Ghia ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Daniela Drummond-Barbosa

Abstract Nutrient availability, stresses, and aging affect tissue stem cells in multicellular organisms; yet, the underlying physiological mechanisms in vivo remains largely unexplored. Dr. Drummond-Barbosa pioneered using Drosophila to study the physiology of tissue stem cell regulation. Her laboratory played a major role in delineating how diet, brain insulin-like peptides, and the TOR nutrient sensor control the germline stem cell (GSC) lineage. They also discovered that adipocyte-specific disruption of amino acid transport, other nutrient signaling, and metabolic pathways causes distinct germline phenotypes. They also showed that nuclear receptors act in multiple tissues to affect the GSC lineage through direct and indirect mechanisms. More recently, her group has been exploring how other physiological stresses affect the GSC lineage. Her group’s studies point to extensive communication between the brain, adipocytes, hepatocyte-like cells, and the germline, and underscore the complexity of the physiological network that modulates stem cell lineage behavior.


Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 697-710 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
M. Shankland

The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 907 ◽  
Author(s):  
Takeshi Motohara ◽  
Hidetaka Katabuchi

Epithelial ovarian cancer is a highly lethal gynecological malignancy that is characterized by the early development of disseminated metastasis. Though ovarian cancer has been generally considered to preferentially metastasize via direct transcoelomic dissemination instead of the hematogenous route, emerging evidence has indicated that the hematogenous spread of cancer cells plays a larger role in ovarian cancer metastasis than previously thought. Considering the distinctive biology of ovarian cancer, an in-depth understanding of the biological and molecular mechanisms that drive metastasis is critical for developing effective therapeutic strategies against this fatal disease. The recent “cancer stem cell theory” postulates that cancer stem cells are principally responsible for tumor initiation, metastasis, and chemotherapy resistance. Even though the hallmarks of ovarian cancer stem cells have not yet been completely elucidated, metastasized ovarian cancer cells, which have a high degree of chemoresistance, seem to manifest cancer stem cell properties and play a key role during relapse at metastatic sites. Herein, we review our current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches.


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