Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

2012 ◽  
Author(s):  
David W. Schomberg
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Hormone Receptor ◽  
Follicle Stimulating Hormone ◽  
Stem Cell Markers ◽  
Ovarian Cancer Stem Cells ◽  
Cell Markers ◽  
Novel Approach

scholarly journals HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Wenxiang Wang ◽  
Yuxia Gao ◽  
Jing Hai ◽  
Jing Yang ◽  
Shufeng Duan
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Drug Sensitivity ◽  
Ovarian Cancer Cells ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Ovarian Cancer Stem Cells

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.

scholarly journals Gastric Cancer Stem Cells Survive in Stress Environments via Their Autophagy System

2020 ◽  
Author(s):  
Shingo Togano ◽  
Masakazu Yashiro ◽  
Go Masuda ◽  
Atsushi Sugimoto ◽  
Yuichiro Miki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Electron Microscope ◽  
Cancer Stem Cells ◽  
Western Blot ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Autophagy Inhibitor ◽  
Stress Environments

Abstract Background: It has been reported that cancer stem cells (CSCs) play an important role in the progression of carcinoma and have a high potential for survival in various stress environments such as starvation and hypoxia. However, the mechanisms responsible for the capacity of CSCs to survive under stresses have been unclear. The aim of this study was to clarify the significance of the autophagy systems of CSCs under stress environments.Methods: Four human gastric cancer cell line, OCUM-12, OCUM-2MD3, MKN-45 and MKN-74 were used. Side population (SP) cells were sorted from the parent OCUM-12 and OCUM-2MD3, as CSC rich cells. The expression of stem cell markers was examined by RT-PCR. The viability of cancer cells under starvation and hypoxia (1%O2) was evaluated by MTT assay with or without the autophagy inhibitor, chloroquine. The expression level of the autophagy molecule LC3-II was examined by western blot. The numbers of autophagosomes and autolysosomes were counted by electron microscope.Results: SP cells of OCUM-12 showed a higher expression of stem cell markers and higher viability in starvation and hypoxia. Western blot and electron microscope examinations indicated that the autophagy was more induced in SP cells than in parent cells. The autophagy inhibitor significantly decreased the viability and the proportion of SP cells under the stress environments.Conclusions: Cancer stem cells of gastric cancer might maintain their viability under stress environments of starvation and hypoxia via the autophagy system. Autophagy inhibitors might be a promising therapeutic agent for gastric cancer.

scholarly journals Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

2014 ◽  
Vol 111 (48) ◽  
pp. 17266-17271 ◽  
Author(s):  
Suping Zhang ◽  
Bing Cui ◽  
Hsien Lai ◽  
Grace Liu ◽  
Emanuela M. Ghia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Therapy ◽  
Cancer Stem Cell ◽  
Stem Cell Therapy ◽  
Ovarian Cancer Stem Cells ◽  
Anti Cancer

Cancer Stem Cells with Overexpression of Neuronal Markers Enhance Chemoresistance and Invasion in Retinoblastoma

2020 ◽  
Vol 20 (9) ◽  
pp. 710-719
Author(s):  
Sekaran Balaji ◽  
Radhakrishnan Santhi ◽  
Usha Kim ◽  
Veerappan Muthukkaruppan ◽  
Chidambaranathan G. Priya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Abc Transporters ◽  
Soft Agar ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Neuronal Markers ◽  
Neuronal Stem Cell

Background: Retinoblastoma is a sight and life-threatening embryonal tumor in children. Though chemotherapy is the main mode of therapy, evolving resistance remains a major obstacle in treatment success. The presence of cancer stem cells (CSC) is frequently reported to be responsible for chemoresistance in multiple tumors. Objective: Our study aims to identify the molecular factors that facilitate the chemoresistance through cancer stem cells in retinoblastoma. Methods: We developed etoposide and carboplatin resistant retinoblastoma (Y79) cell lines by stepwise drug increment treatment, validated with MTT and TUNEL assays. Colony forming and invasive ability were studied by soft-agar colony forming and transwell assays, respectively. Similar analysis in non-responsive retinoblastoma tumors were carried out by histopathology. Finally, expression of CSC/neuronal markers and ABC transporters were examined by quantitative PCR and protein expression of neuronal stem cell markers was confirmed by Western blot. Results: Larger colony size of resistant cells in soft-agar assay provided evidence for increased selfrenewability. Histopathology in non-responsive tumors showed poorly differentiated cells predominantly. Besides, both resistant cell lines and non-responsive tumors showed increased invasion with higher expression of neuronal stem cell markers - SOX2, NANOG, OCT4 and ABC transporters - ABCB1 and ABCC3. Increased self-renewal ability and invasion along with overexpression of stemness markers in resistant cells and tumors provide evidence for stemness driving chemoresistance and invasion in retinoblastoma. Conclusion: We have demonstrated Neuronal stem cell/CSC markers that facilitate the maintenance of cancer stem cells. Developing therapies targeting these factors will help in overcoming resistance and improving retinoblastoma treatment.

Expression of stem cell markers in pancreatic ductal adenocarcinoma and clinical relevance.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15058-e15058
Author(s):  
Kalliopi Andrikou ◽  
Luca Faloppi ◽  
Cristian Loretelli ◽  
Alessandra Mandolesi ◽  
Italo Bearzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Human Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Small Subset ◽  
Stem Cell Markers ◽  
Cell Markers

e15058 Background: Emerging evidence has suggested that malignant tumors are heterogeneous and that are composed of a small subset of distinct cancer cells (usually defined by cell surface marker expression) that are responsible for tumor initiation and propagation, termed cancer stem cells. These cancer stem cells (CSCs), or tumor-initiating cells (TICs), exhibit properties of normal stem cells and are associated with resistance to current therapies. It was found that human pancreatic cancer has shown a population of cancer stem cells that have aberrantly activated developmental signaling pathways, are resistant to standard chemotherapy and radiation, and have up-regulated signaling cascades that are integral for tumor metastasis. The aim of our study is to investigate the prognostic implication of cancer stem cell markers in pancreatic ductal adenocarcinoma. Methods: In 43 histological samples of pancreatic ductal adenocarcinoma were performed molecular biology assessment of CD 24, CD44, CD133, CD166, OCT3/4, LGR5. Results: At univariate analysis patients with an overexpression of CD44, CD133, OCT3/4 showed a worse prognosis in terms of overall survival (respectively: p=0.031; p=0.014; p=0.001). At multivariate analysis OCT3/4 resulted to be independent factor influencing outcome (HR=0.23). Patients with overexpression of all factors seem to have a worse OS compared to patients expressing only two, one or none (8.6 vs. 15.6 vs. 18.0 vs. 59.9 mts; p=0.006). Conclusions: Our data suggest that the presence of cancer stem cells could be linked with tumor aggressiveness and patients’ survival. This finding could drive therapeutic decision towards less or more intensive treatment.

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