Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment

Abstract Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.

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Effect of Delay on Selection Dynamics in Long-Term Sphere Culture of Cancer Stem Cells

Discrete Dynamics in Nature and Society ◽

10.1155/2013/606250 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5

Author(s):

Peng Tang ◽

Aijun Fan ◽

Jianquan Li ◽

Jun Jiang ◽

Kaifa Wang

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Time Delay ◽

Cancer Stem Cells ◽

Cell Populations ◽

Delay Effect ◽

Selection Dynamics ◽

Sphere Culture ◽

Theoretical Results

To quantitatively study the effect of delay on selection dynamics in long-term sphere culture of cancer stem cells (CSCs), a selection dynamic model with time delay is proposed. Theoretical results show that the ubiquitous time delay in cell proliferation may be one of the important factors to induce fluctuation, and numerical simulations indicate that the proposed selection dynamical model with time delay can provide a better fitting effect for the experiment of a long-term sphere culture of CSCs. Thus, it is valuable to consider the delay effect in the future study on the dynamics of nongenetic heterogeneity of clonal cell populations.

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Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

Bone ◽

10.1016/j.bone.2013.12.021 ◽

2014 ◽

Vol 60 ◽

pp. 198-212 ◽

Cited By ~ 23

Author(s):

Riccardo Di Fiore ◽

Michela Marcatti ◽

Rosa Drago-Ferrante ◽

Antonella D'Anneo ◽

Michela Giuliano ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Mutant P53 ◽

Gain Of Function ◽

Human Osteosarcoma ◽

Mg63 Cells

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

International Journal of Oncology ◽

10.3892/ijo.2014.2618 ◽

2014 ◽

Vol 45 (5) ◽

pp. 2013-2023 ◽

Cited By ~ 39

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

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Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly

Theranostics ◽

10.7150/thno.20771 ◽

2017 ◽

Vol 7 (19) ◽

pp. 4805-4824 ◽

Cited By ~ 22

Author(s):

Xiaoti Lin ◽

Weiyu Chen ◽

Fengqin Wei ◽

Binhua P. Zhou ◽

Mien-Chie Hung ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Breast Cancer Stem Cells ◽

Nanoparticle Delivery

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Oncogenic RAS Generates Cancer Stem Cells in p53-Deficient Fibroblasts Through SOX2 Induced By CDK1-Mediated Protein O-GlcNAcylation

10.21203/rs.3.rs-981157/v1 ◽

2021 ◽

Author(s):

Masahiro Shimizu ◽

Hiroshi Shibuya ◽

Nobuyuki Tanaka

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Gene Knockout ◽

Human Fibroblasts ◽

Signalling Pathway ◽

Oncogenic Ras ◽

Primary Mouse ◽

Underlying Mechanisms ◽

Tumour Initiation

Abstract Cancer stem cells (CSCs) have tumour initiation, self-renewal, and long-term tumour repopulation properties, and it is postulated that differentiated somatic cells can be reprogrammed to CSCs by oncogenic signals. We previously showed that oncogenic HRASV12 conferred tumour initiation capacity in tumour suppressor p53-deficient (p53−/−) primary mouse embryonic fibroblasts (MEFs) through transcription factor NF-κB-mediated enhancement of glucose uptake; however, the underlying mechanisms of RAS oncogene-induced CSC reprogramming have not been elucidated. Here, we found that the expression of the reprogramming factor SOX2 was induced by HRASV12 in p53−/− MEFs. Moreover, gene knockout studies revealed that SOX2 is an essential factor for the generation of CSCs by HRASV12 in mouse and human fibroblasts. We demonstrated that HRASV12-induced cyclin-dependent kinase 1 (CDK1) activity and subsequent enhancement of protein O-GlcNAcylation were required for SOX2 induction and CSC generation in these fibroblasts and cancer cell lines containing RAS mutations. Moreover, the CDK inhibitor dinaciclib and O-GlcNAcylation inhibitor OSMI1 reduced the number of CSCs derived from these cells. Taken together, our results reveal a signalling pathway and mechanism for CSC generation by oncogenic RAS and suggest the possibility that this signalling pathway is a therapeutic target for CSCs.

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