Prognostic Impact of the Cancer Stem Cell–Related Marker NANOG in Ovarian Serous Carcinoma

Lee, Maria; Nam, Eun Ji; Kim, Sang Wun; Kim, Sung Hoon; Kim, Jae-Hoon; Kim, Young Tae

doi:10.1097/igj.0b013e3182738307

Cited by 59 publications

(48 citation statements)

References 30 publications

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“…We examined the changes in protein levels of these factors and found that Nanog levels increase in TIC culture conditions, in agreement with others 13,35 as well as CD133, TRA-1-60, and CD117. A human stem cell marker cDNA array further showed an increase in CD133, Nanog, Melk, and PODXL genes in the TIC conditions compared to traditional adherent conditions.…”

Section: Representative Resultssupporting

confidence: 89%

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

House¹,

Hernandez²,

Annunziata³

2015

JoVE

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Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent 'floater' cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential.Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse.

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Section: Representative Resultssupporting

confidence: 89%

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

House¹,

Hernandez²,

Annunziata³

2015

JoVE

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“…It has been known that CSC characteristics may lead to cancer aggressiveness, chemoresistance to anticancer drugs, and a high risk of recurrence in patients with cancer (29,31,32,43). Recent reports suggest that tumorigenicity and tumor progression is driven by CSC characteristics, and CSCs consistently showed elevated EZH2 and SUZ12 expression (24)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

“…S8). Furthermore, mRNA levels of CD44, KLF4, OCT4, and ABCG2 known as CSC markers (29)(30)(31)(32) significantly affected in under MMC-or cisplatin-treated conditions in bladder cancer cells with altered E2F1, EZH2, and SUZ12 expression than in matched control group ( Fig. 6D and Supplementary Fig.…”

Section: Characterization Of Bladder Cancer Cell Lines By Unsupervisementioning

confidence: 95%

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Lee

Roh

Kim

et al. 2015

Clinical Cancer Research

111

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Purpose: Previous study identified E2F1 as a key mediator of non-muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis and aggressive characteristics of bladder cancer.Experimental Design: Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay.Results: The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)-related genes.Conclusions: The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1--EZH2--SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1-EZH2-SUZ12-driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities. Clin Cancer Res; 21(23); 5391-403. Ó2015 AACR.

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“…being expressed predominantly in the less differentiated but extremely treatment-sensitive subtypes seminoma and embryonal carcinoma [60]. In contrast, in breast and ovarian cancers, high expression of Nanog correlated with poor survival [61,62]. As a consequence, the potential of targeting stem-like features of cancer cells particularly in GCTs remains questionable.…”

Section: Targeting Cancer Stem Cellsmentioning

confidence: 88%

Investigational targeted therapies for the treatment of testicular germ cell tumors

Oing

Kollmannsberger

Bokemeyer

2016

Expert Opinion on Investigational Drugs

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Prognostic Impact of the Cancer Stem Cell–Related Marker NANOG in Ovarian Serous Carcinoma

Abstract: Positive NANOG expression is associated with poor prognosis of ovarian serous carcinoma. NANOG has potential as a predictor of survival for patients with ovarian carcinomas and may be involved in the mechanism of chemoresistance.

Cited by 59 publications

References 30 publications

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

<em>In vitro</em> Enrichment of Ovarian Cancer Tumor-initiating Cells

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Investigational targeted therapies for the treatment of testicular germ cell tumors

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