417. In vivo and in vitro evidence for cancer stem cells in human endometrial cancer

2008 ◽  
Vol 20 (9) ◽  
pp. 97
Author(s):  
S. Hubbard ◽  
C. E. Gargett
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Type I ◽  
Type Ii ◽  
Cloning Efficiency ◽  
Isolated Cells ◽  
Vimentin Expression ◽  
Self Renewal

Cancer stem cells (CSCs) have been identified in solid human cancers, including breast, colon, and ovary. Recent evidence suggests that the highly regenerative human endometrium harbors rare populations of epithelial stem/progenitor cells1. We hypothesised that CSCs are responsible for the epithelial neoplasia associated with endometrial carcinoma (EC), the most common gynaecological malignancy in women. The aim of this study was to demonstrate that a rare population of EC cells posses CSC properties. Stem cell characteristics were assessed in 25 EC and 2 endometrial hyperplasia tissues obtained from women aged 62 ± 9 yrs. Samples were cultured at clonal densities (100–500 cells/cm2) for 3–5 wks to determine cloning efficiency. Individual clones were serially subcloned (<10 cells/cm2) every 2–4 wks to determine self renewal capacity. Isolated cells in serial dilution (103–106 cells) were placed under the kidney capsule of immunocompromised mice for 12–16 wks to examine for the presence of tumour initiating cells (TIC). Resulting tumours and original parent tumours were examined for markers by immunohistochemistry. Most samples (23/26) contained rare colony forming cells. The cloning efficiency was 0.23% ± 0.28% (n = 11) in G1, 0.78% ± 0.67% (n = 8) in G2, 0.22% ± 0.21% (n = 3) in G3, 0.03% (n = 2) in type II tumours, and 0.14% (n = 2) in hyperplasia samples, and did not differ significantly between grades or between type I EC and normal endometrial epithelial samples 1. Single cell derived clones subcloned 2.5 ± 1.4 (n = 11), 3.2 ± 0.4 (n = 5), 3.5 (n = 2), 3.0 ± 1.7 (n = 3), and 2.5 (n = 2) times in G1, G2, G3, type II tumours and hyperplasia samples respectively, indicating increasing self renewal capacity with increasing tumour grade. Transplanted EC single cell suspensions initiated tumour growth with similar morphology, ERα, PR, EpCAM, cytokeratin, and vimentin expression as the parent tumour, indicating the presence of TIC. This evidence suggests that rare cells possessing the CSC properties of clonogenicty, self renewal, and tumorigenicity, may be responsible for the initiation and progression of EC. (1) Chan RWS et al. (2004). Biology of Reproduction. 70:1738–1750

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 Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Shui Ma ◽  
Xiao-Li Yang ◽  
Yu-Shan Liu ◽  
Hua Ding ◽  
Jian-Jun Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Loss Of Function ◽  
Self Renewal

Abstract Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

scholarly journals Chemosensitization of prostate cancer stem cells in mice by angiogenin and plexin-B2 inhibitors

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Shuping Li ◽  
Kevin A. Goncalves ◽  
Baiqing Lyu ◽  
Liang Yuan ◽  
Guo-fu Hu
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ribosomal Rna ◽  
Protein Translation ◽  
Chemotherapeutic Agents ◽  
Self Renewal ◽  
5S Ribosomal Rna ◽  
Prostate Cancer Stem Cells

AbstractCancer stem cells (CSCs) are an obstacle in cancer therapy and are a major cause of drug resistance, cancer recurrence, and metastasis. Available treatments, targeting proliferating cancer cells, are not effective in eliminating quiescent CSCs. Identification of CSC regulators will help design therapeutic strategies to sensitize drug-resistant CSCs for chemo-eradication. Here, we show that angiogenin and plexin-B2 regulate the stemness of prostate CSCs, and that inhibitors of angiogenin/plexin-B2 sensitize prostate CSCs to chemotherapy. Prostate CSCs capable of self-renewal, differentiation, and tumor initiation with a single cell inoculation were identified and shown to be regulated by angiogenin/plexin-B2 that promotes quiescence and self-renewal through 5S ribosomal RNA processing and generation of the bioactive 3′-end fragments of 5S ribosomal RNA, which suppress protein translation and restrict cell cycling. Monoclonal antibodies of angiogenin and plexin-B2 decrease the stemness of prostate CSCs and sensitize them to chemotherapeutic agents in vitro and in vivo.

scholarly journals MicroRNA-29b-1 impairs in vitro cell proliferation, self-renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells

2014 ◽  
Vol 45 (5) ◽  
pp. 2013-2023 ◽  
Author(s):  
RICCARDO DI FIORE ◽  
ROSA DRAGO-FERRANTE ◽  
FRANCESCA PENTIMALLI ◽  
DOMENICO DI MARZO ◽  
IRIS MARIA FORTE ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Self Renewal ◽  
Human Osteosarcoma

scholarly journals THE TRANSFORMATION OF PNEUMOCOCCAL TYPES

1930 ◽  
Vol 51 (1) ◽  
pp. 123-147 ◽  
Author(s):  
Martin H. Dawson
Keyword(s):  
Single Cell ◽  
Subcutaneous Injection ◽  
Intermediate Stage ◽  
Group Iv ◽  
Type I ◽  
Type Ii ◽  
Type Iii

1. Type-specific S pneumococci may be transformed from one specific S type into other specific S types through the intermediate stage of the R form. 2. R forms of pneumococi, derived from any specific S type, may be transformed into S organisms of other specific types by the following procedure:—The subcutaneous injection, in white mice, of small amounts of living R forms together with vaccines of heterologous S cultures. (i) S vaccines heated for 15' at temperatures between 60° and 80°C., are effective in causing R forms, derived from heterologous S types, to revert to the type of the vaccine. (ii) S vaccines heated for 15' at temperatures between 80° and 100°C., are not effective in causing R forms, derived from heterologous S types, to revert to the type of the vaccine. (iii) S vaccines heated for 15' at temperatures between 80° and 100°C., may cause 2 R and 3 R cultures to revert to their original S type. (iv) S vaccines of any type, including Type I, heated for 15' at temperatures between 80° and 100°C., are not effective in causing 1 R cultures to revert to their original S type. (v) S vaccines heated for periods as long as two hours at 60°C. are effective in causing R forms, derived from heterologous types, to revert to the type of the vaccine. 3. A single cell R strain, derived from a Type II S pneumococcus, has been successively transformed into a Type III S, a Type I S and a Group IV S culture. 4. Corresponding with the various degrees of "degradation" of the R form there are varying degrees of "development" of the S form. 5. The nature of the conditions responsible for alteration of type as induced by these procedures has been investigated and the causes responsible for the transformations are discussed. 6. All attempts to produce transformation of type in vitro have been unsuccessful. 7. The rô1e which the phenomenon of transformation of type may play in problems of infection and epidemiology is indicated.

scholarly journals Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells

2017 ◽  
Vol 71 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Zhao Yang ◽  
Chong Li ◽  
Zusen Fan ◽  
Hongjie Liu ◽  
Xiaolong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Cancer Stem Cells ◽  
Single Cell ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Self Renewal ◽  
Single Cell Sequencing

Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves

2008 ◽  
Vol 294 (4) ◽  
pp. H1767-H1778 ◽  
Author(s):  
M. Pho ◽  
W. Lee ◽  
D. R. Watt ◽  
C. Laschinger ◽  
C. A. Simmons ◽  
...  
Keyword(s):  
Stem Cells ◽  
Side Population ◽  
Smooth Muscle Actin ◽  
Tensile Force ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Side Population Cells ◽  
Isolated Cells ◽  
Color Flow

The formation of myofibroblasts in valve interstitial cell (VIC) populations contributes to fibrotic valvular disease. We examined myofibroblast differentiation in VICs from porcine aortic valves. In normal valves, cells immunostained for α-smooth muscle actin (α-SMA, a myofibroblast marker) were rare (0.69 ± 0.48%), but in sclerotic valves of animals fed an atherogenic diet, myofibroblasts were spatially clustered and abundant (31.2 ± 6.3%). In cultured VIC populations from normal valves, SMA-positive myofibroblasts were also spatially clustered, abundant (21% positive cells after 1 passage), and stained for collagen type I and vimentin but not desmin. For an analysis of stem cells, two-color flow cytometry of isolated cells stained with Hoechst 33342 demonstrated that 0.5% of VICs were side population cells; none stained for SMA. Upon culture, sorted side population cells generated ∼85% SMA-positive cells, indicating that some myofibroblasts originate from a rare population with stem cell characteristics. Plating cells on rigid collagen substrates enabled the formation of myofibroblasts after 5 days in culture, which was completely blocked by culture of cells on compliant collagen substrates. Exogenous tensile force also significantly increased SMA expression in VICs. Isotope-coded affinity tags and mass spectrometry were used to identify differentially expressed proteins in myofibroblast differentiation of VICs. Of the nine proteins that were identified, cofilin expression and phospho-cofilin were strongly increased by conditions favoring myofibroblast differentiation. Knockdown of cofilin with small-interfering RNA inhibited collagen gel contraction and reduced myofibroblast differentiation as assessed by the SMA incorporation into stress fibers. When compared with normal valves, diseased valves showed strong immunostaining for cofilin that colocalized with SMA in clustered cells. We conclude that in VICs, cofilin is a marker for myofibroblasts in vivo and in vitro that arise from a rare population of stem cells and require a rigid matrix for formation.

scholarly journals IL-17B/IL-17RB signaling cascade contributes to self-renewal and tumorigenesis of cancer stem cells by regulating Beclin-1 ubiquitination

Oncogene ◽  
2021 ◽  
Author(s):  
Qingli Bie ◽  
Hui Song ◽  
Xinke Chen ◽  
Xiao Yang ◽  
Shuo Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Tumor Necrosis Factor Receptor ◽  
Beclin 1 ◽  
Signaling Cascade ◽  
Interleukin 17 ◽  
Self Renewal

AbstractCancer stem cells (CSCs) are characterized by robust self-renewal and tumorigenesis and are responsible for metastasis, drug resistance, and angiogenesis. However, the molecular mechanisms for the regulation of CSC homeostasis are incompletely understood. This study demonstrated that the interleukin-17 (IL-17)B/IL-17RB signaling cascade promotes the self-renewal and tumorigenesis of CSCs by inducing Beclin-1 ubiquitination. We found that IL-17RB expression was significantly upregulated in spheroid cells and Lgr5-positive cells from the same tumor tissues of patients with gastric cancer (GC), which was closely correlated with the degree of cancer cell differentiation. Recombinant IL-17B (rIL-17B) promoted the sphere-formation ability of CSCs in vitro and enhanced tumor growth and metastasis in vivo. Interestingly, IL-17B induced autophagosome formation and cleavage-mediated transformation of LC3 in CSCs and 293T cells. Furthermore, inhibition of autophagy activation by ATG7 knockdown reversed rIL-17B-induced self-renewal of GC cells. In addition, we showed that IL-17B also promoted K63-mediated ubiquitination of Beclin-1 by mediating the binding of tumor necrosis factor receptor-associated factor 6 to Beclin-1. Silencing IL-17RB expression abrogated the effects of IL-17B on Beclin-1 ubiquitination and autophagy activation in GC cells. Finally, we showed that IL-17B level in the serum of GC patients was positively correlated with IL-17RB expression in GC tissues, and IL-17B could induce IL-17RB expression in GC cells. Overall, the results elucidate the novel functions of IL-17B for CSCs and suggest that the intervention of the IL-17B/IL-17RB signaling pathway may provide new therapeutic targets for the treatment of cancer.

scholarly journals Correlation between CD44+ cancer stem cell expression and histopathological types of nasopharyngeal carcinoma

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 678
Author(s):  
Muhtarum Yusuf ◽  
Indriyadevi Indra ◽  
Sri Herawati Juniati ◽  
Yussy Afriani Dewi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Nasopharyngeal Carcinoma ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Response To Treatment ◽  
Type I ◽  
Type Ii ◽  
Cd44 Expression ◽  
Cell Expression

Background: Nasopharyngeal carcinoma (NPC) recurrency rate is still high despite patients receiving complete treatment. The response to treatment may vary depending on the type of histopathology and Epstein-Barr virus, however the mechanism remains unclear. Recent studies have found that there is a relationship between response to treatment and the presence of cancer stem cells (CSCs). CD44+ cancer stem cells may cause cancer cells to be resistant to treatment. Therefore, this cross-sectional study aims to determine the correlation between CD44 + cancer stem cell expression and the histopathological types of NPC. Method: Samples were obtained from NPC biopsies of type I, II, III patients (based on WHO histopathology criteria), who had not received prior treatment. CD44+ expression was examined using immunohistochemistry methods by staining CD44+ monoclonal antibodies. The degree of CD44+ cell membrane expression was based on the immunoreactive score scale or the Remmele index scale. Results: Most histopathological types were WHO type III (21 patients, 50%), followed by type II (18 patients, 42.86%), and type I (3 patients, 7.14%). CD44 + expression on type I showed one patient had moderate positive and two patients had a high-positive expression. In type II, 10 were moderate positive and eight were high-positive. In type III, one patient was low-positive, 11 were moderate positive and nine patients were high-positive. Statistical analysis showed that the CD44+ expression difference between the three histopathology types were not statistically significant. Conclusion: There were no correlations between CD44 + expression and histopathological type of NPC.

scholarly journals Moonlighting Role of PEDF in Breast Cancer

2020 ◽  
Author(s):  
Carmen Gil-Gas ◽  
Marta Sánchez-Díez ◽  
Paloma Honrubia-Gómez ◽  
Jose Luis Sánchez-Sánchez ◽  
Carmen Belen Alvarez-Simón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Patient ◽  
In Vitro Culture ◽  
Screening Tests ◽  
Stem Cell Markers ◽  
Self Renewal

Abstract Background: Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates still remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods: We have designed a transgenic protein consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Present work is based in doses-response in vitro assays as well as flow cytometry analysis of surface markers and cell cycle kinetic study of the tumour initiating cells.Results: In this study we show that this type of cells is present not only in cancer cell lines but also in cancer cells from patients with metastatic and advanced stage tumours. We also present new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, expression of markers, and carcinogenicity of cancer stem cells. This protein has been involved in self-renewal in adult stem cells and has been described as anti-tumoral because of its anti-angiogenic effect. However, we show that PEDF enhances resistance in breast cancer patient cells in vitro culture by favoring a slow cellular cycle population (LT+). The PEDF signalling pathway could be a useful tool for controlling cancer stem cells self-renewal, and therefore control patient relapse. Conclusions: We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in vitro culture. We have also demonstrated that this PEDF modified protein produces a significant decrease in cancer stem cell markers. All these properties make this protein a potential application in clinical cancer therapies via co-administration with chemotherapy for relapse cancer treatment.

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