scholarly journals Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells

2007 ◽  
Vol 11 (1) ◽  
pp. 32-39 ◽  
Author(s):  
J Miki ◽  
J S Rhim
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cultures ◽  
In Vitro Models ◽  
Prostate Cell

Demonstration of subpopulations with differing cancer stem cell phenotypes in xenograft and in vitro models of colorectal liver metastases.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 394-394
Author(s):  
Dominic E. Sanford ◽  
Andrew Giorgi ◽  
Brian D. Goetz ◽  
Roheena Z. Panni ◽  
William G. Hawkins ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Metastases ◽  
In Vitro Models ◽  
Model Systems ◽  
Cell Populations ◽  
Tumor Initiating Cells ◽  
Distinct Cell

394 Background: Tumors are composed of heterogeneous cell populations, some of which demonstrate enhanced tumor-forming capabilities (so-called tumor initiating cells [TIC] or cancer stem cells). In colorectal cancer (CRC), CD133, 44, and 24 are cell surface markers that identify TIC. Therefore, we sought to determine if CRC liver metastases (CRC-LM) form xenografts (in vivo) and cell cultures (in vitro) with TIC markers. Methods: CRC-LM were grafted in NOD/SCID mice and passaged serially. Xenografts were mechanically dissociated and cultured under sphere forming conditions. Flow cytometry was performed for TIC phenotype. Results: 16 of 18 (89%) CRC-LM specimens formed tumors in mice. Xenografts formed EpCAM+ tumors and spheres. The frequency of CD133+, CD44+, and CD133+/CD44+ tumor cells were 55%, 33%, and 23%, respectively. There was a subpopulation of CD133+/CD44+ cells with elevated CD44 expression(CD44hi). This CD133+/CD44hi population was also CD24+; representing 5% of cells. Eight of eleven (73%) xenografts formed spheres in vitro. The frequency of CD133+, CD44+, and CD133+/CD44+ cells were 63%, 47%, and 26%, respectively. CD133+/CD44+/CD24+ cells made up 8% of sphere-forming cells. There was a non-significant trend towards increased frequency of CD133+, CD44+, and CD133/CD44 positive cells in the spheres compared to the xenografts. However, the percentage of CD133+/CD44+/CD24+ cells was significantly increased in spheres relative to xenografts (8% vs. 5%, respectively; p<0.05) (see Table). Conclusions: CRC-LM derived xenografts and spheres are composed of distinct cell populations with differing levels of TIC/cancer stem cells. Sphere cultures may enhance for the most enriched TIC population. Thus, xenografts and sphere cultures are important model systems to further study the importance of cancer stem cells in CRC progression and metastases. [Table: see text]

scholarly journals In vitro models of cancer stem cells and clinical applications

BMC Cancer ◽  
2016 ◽  
Vol 16 (S2) ◽  
Author(s):  
Sara S. Franco ◽  
Karolina Szczesna ◽  
Maria S. Iliou ◽  
Mohammed Al-Qahtani ◽  
Ali Mobasheri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
In Vitro Models ◽  
Clinical Applications

scholarly journals Salinomycin Exerts Anticancer Effects on PC-3 Cells and PC-3-Derived Cancer Stem Cells In Vitro and In Vivo

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yunsheng Zhang ◽  
Luogen Liu ◽  
Fang Li ◽  
Tao Wu ◽  
Hongtao Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Xenograft Model ◽  
Mechanistic Study ◽  
Prostate Cell ◽  
Downstream Target ◽  
Prostate Cancer Stem Cells

Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs). However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells. An in vivo experiment confirmed that salinomycin suppressed tumorigenesis in a NOD/SCID mice xenograft model generated from implanted PC-3 cells by inhibiting the Wnt/β-catenin pathway, since the total β-catenin protein level was reduced and the downstream target c-Myc level was significantly downregulated. We also showed that salinomycin, but not paclitaxel, triggered more apoptosis in aldehyde dehydrogenase- (ALDH-) positive PC-3 cells, which were considered as the prostate cancer stem cells, suggesting that salinomycin may be a promising chemotherapeutic to target CSCs. In conclusion, this study suggests that salinomycin reduces resistance and relapse of prostate tumor by killing cancer cells as well as CSCs.

Basic Issues on Cancer Stem Cells-Concept, In vitro Models and Therapeutic Implications

Niche Journal ◽  
2012 ◽  
Vol 1 (1) ◽  
pp. 17-20
Author(s):  
Oya Topaloglu ◽  
Mustafa Sahin ◽  
Tuncay Delibasi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
In Vitro Models ◽  
Therapeutic Implications

Stem Cells as In Vitro Models of Disease

2007 ◽  
Vol 2 (4) ◽  
pp. 280-292 ◽  
Author(s):  
Pilar Ruiz-Lozano ◽  
Prithi Rajan
Keyword(s):  
Stem Cells ◽  
In Vitro Models ◽  
Models Of Disease

scholarly journals STEM-26. SMALL MOLECULE DRUG CBL0137 INHIBITS THE FACT COMPLEX AND SENSITIZES GLIOBLASTOMA CANCER STEM CELLS TO RADIOTHERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii201-ii202
Author(s):  
Miranda Tallman ◽  
Abigail Zalenski ◽  
Amanda Deighen ◽  
Morgan Schrock ◽  
Sherry Mortach ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
High Rate ◽  
Orthotopic Model ◽  
In Vivo Models ◽  
Specific Cytotoxicity ◽  
Treatment Paradigm ◽  
Cancer Agent

Abstract Glioblastoma (GBM) is a malignant brain tumor with nearly universal recurrence. GBM cancer stem cells (CSCs), a subpopulation of radio- and chemo-resistant cancer cells capable of self-renewal, contribute to the high rate of recurrence. The anti-cancer agent, CBL0137, inhibits the FACT (facilitates chromatin transcription) complex leading to cancer cell specific cytotoxicity. Here, we show that CBL0137 sensitized GBM CSCs to radiotherapy using both in vitro and in vivo models. Treatment of CBL0137 combined with radiotherapy led to increased DNA damage in GBM patient specimens and failure to resolve the damage led to decreased cell viability. Using clonogenic assays, we confirmed that CBL0137 radiosensitized the CSCs. To validate that combination therapy impacted CSCs, we used an in vivo subcutaneous model and showed a decrease in the frequency of cancer stem cells present in tumors as well as decreased tumor volume. Using an orthotopic model of GBM, we confirmed that treatment with CBL0137 followed by radiotherapy led to significantly increased survival compared to either treatment alone. Radiotherapy remains a critical component of patient care for GBM, even though there exists a resistant subpopulation. Radio-sensitizing agents, including CBL0137, pose an exciting treatment paradigm to increase the efficacy of irradiation, especially by inclusively targeting CSCs.

scholarly journals Aspirin enhances the therapeutic efficacy of cisplatin in oesophageal squamous cell carcinoma by inhibition of putative cancer stem cells

2021 ◽  
Author(s):  
Zhigeng Zou ◽  
Wei Zheng ◽  
Hongjun Fan ◽  
Guodong Deng ◽  
Shih-Hsin Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
High Throughput Sequencing ◽  
Combined Treatment ◽  
Oesophageal Squamous Cell Carcinoma

Abstract Background Cancer stem cells (CSCs) are related to the patient’s prognosis, recurrence and therapy resistance in oesophageal squamous cell carcinoma (ESCC). Although increasing evidence suggests that aspirin (acetylsalicylic acid, ASA) could lower the incidence and improve the prognosis of ESCC, the mechanism(s) remains to be fully understood. Methods We investigated the role of ASA in chemotherapy/chemoprevention in human ESCC cell lines and an N-nitrosomethylbenzylamine-induced rat ESCC carcinogenesis model. The effects of combined treatment with ASA/cisplatin on ESCC cell lines were examined in vitro and in vivo. Sphere-forming cells enriched with putative CSCs (pCSCs) were used to investigate the effect of ASA in CSCs. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed to determine the alterations in chromatin accessibility caused by ASA in ESCC cells. Results ASA inhibits the CSC properties and enhances cisplatin treatment in human ESCC cells. ATAC-seq indicates that ASA treatment results in remarkable epigenetic alterations on chromatin in ESCC cells, especially their pCSCs, through the modification of histone acetylation levels. The epigenetic changes activate Bim expression and promote cell death in CSCs of ESCC. Furthermore, ASA prevents the carcinogenesis of NMBzA-induced ESCC in the rat model. Conclusions ASA could be a potential chemotherapeutic adjuvant and chemopreventive drug for ESCC treatment.

Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

1988 ◽  
Vol 16 (1) ◽  
pp. 32-37
Author(s):  
Margherita Ferro ◽  
Anna Maria Bassi ◽  
Giorgio Nanni
Keyword(s):  
Cell Lines ◽  
Cell Cultures ◽  
Membrane Lipids ◽  
Hepatoma Cell ◽  
Positive Control ◽  
In Vitro Models ◽  
Low Concentrations ◽  
Formation Efficiency ◽  
Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

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