Caution over use of ES2 as a model of ovarian clear cell carcinoma

Kwok, Angie L M; Wong, Oscar Gee‐Wan; Wong, Eric T.T.; Tsun, Obe K. L.; Chan, Ka‐Kui; Cheung, Annie N.Y.

doi:10.1136/jclinpath-2014-202430

Cited by 20 publications

(17 citation statements)

References 8 publications

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“…39,40 The OVCA429 line was established from a late-stage serous carcinoma as described by Bast et al 41 The ES2 line has been described as a clear cell carcinoma line but has been recently reported to be more reflective of high-grade serous carcinoma. 40,42 Although parental ES2 cells express very little DLX4, the high endogenous CD44 levels in ajp.amjpathol.org -The American Journal of Pathology these cells might explain, in part, the aggressive behavior of this line in xenograft models. At the present time, we can only speculate as to the mechanisms that cause overexpression of DLX4 in ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

The Homeoprotein DLX4 Stimulates NF-κB Activation and CD44-Mediated Tumor–Mesothelial Cell Interactions in Ovarian Cancer

Haria

Trinh

et al. 2015

The American Journal of Pathology

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Ovarian cancers often highly express inflammatory cytokines and form implants throughout the peritoneal cavity. However, the mechanisms that drive inflammatory signaling and peritoneal metastasis of ovarian cancer are poorly understood. We previously identified that high expression of DLX4, a transcription factor encoded by a homeobox gene, is associated with reduced survival of ovarian cancer patients. In this study, we identified that DLX4 stimulates attachment of ovarian tumor cells to peritoneal mesothelial cells in vitro and increases the numbers of peritoneal implants in xenograft models. DLX4 induced expression of the cell surface molecule CD44 in ovarian tumor cells, and inhibition of CD44 abrogated the ability of DLX4 to stimulate tumor-mesothelial cell interactions. The induction of CD44 by DLX4 was attributed to increased activity of NF-κB that was stimulated by the inflammatory cytokine IL-1β, a transcriptional target of DLX4. The stimulatory effects of DLX4 on CD44 levels and tumor-mesothelial cell interactions were abrogated when IL-1β or NF-κB was inhibited in tumor cells. Furthermore, DLX4 expression levels strongly correlated with NF-κB activation and disease stage in clinical specimens of ovarian cancer. Collectively, these findings indicate that DLX4 induces CD44 by stimulating IL-1β-mediated NF-κB activity, thereby promoting peritoneal metastasis of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

The Homeoprotein DLX4 Stimulates NF-κB Activation and CD44-Mediated Tumor–Mesothelial Cell Interactions in Ovarian Cancer

Haria

Trinh

et al. 2015

The American Journal of Pathology

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“…In line with the previous studies, our study showed that the up-regulated DEGs, CDK6 and MDM2 were identified to be involved in p53 signaling pathway, suggesting that miR-22 may play a critical role in ovarian cancer through regulating the p53 signaling pathway. It is worthy of note, however, that the ES-2 used as described in the original study [16], a widely recognized CCOC cell line, was originally established from a poorly differentiated CCOC, which was derived from the surgical tumor specimen of a 47-year-old black woman [43]. Although TP53 mutations in CCOC are rare, a study demonstrated that ES2 was the only CCOC cell line harboring a missense mutation in TP53 (c. 722C>T, p.S241F) [44].…”

Section: Discussionmentioning

confidence: 99%

“…Although TP53 mutations in CCOC are rare, a study demonstrated that ES2 was the only CCOC cell line harboring a missense mutation in TP53 (c. 722C>T, p.S241F) [44]. Therefore, this cell line should be used with caution as a valid model for studying CCOC [43]. Nevertheless, evidence shows high incidence of p53 gene mutation in human OC, which is associated with nuclear accumulation of p53 protein and tumor DNA aneuploidy [45].…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling analysis of the role of miR-22 in clear cell ovarian cancer

Zhen¹,

Guo²,

Xu³

et al. 2016

neo

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This study aimed to investigate the role and potential mechanism of miR-22 in clear cell ovarian cancer (CCOC) progression. The gene expression profile of GSE16568, including 3 CCOC samples with miR-22 overexpression and 3 negative controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed by using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Besides, the miR-22 -mRNA interaction pairs were predicted to explore the critical genes involved in the cancer. Totally, 95 up-regulated DEGs and 51 down-regulated DEGs were identified. The DEGs were enriched in different GO terms and pathways. The up-regulated genes cyclin-dependent kinases (CDK6), MDM2 oncogene, E3 ubiquitin protein ligase (MDM2), and thrombospondin 1 (THBS1) were involved in the p53 signaling pathway. The up-regulated gene FBJ murine osteosarcoma viral oncogene homolog (FOS) was a hub protein in the PPI network of the DEGs. The down-regulated DEGs including lymphoid enhancer-binding factor 1 (LEF1) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were mainly associated with immunity. Nine DEGs as target genes were identified to be recognized by miR-22. Our study suggested that several key genes such as CDK6, MDM2, LEF1, MYB, and FOS that involved in different pathways including p53 signaling pathway were associated with CCOC progression. miR-22 may play an essential role in cell migration and invasion in CCOC through targeting responsive genes.

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“…Therefore, it is important to thoroughly investigate the immunohistochemical and mutational profile of the used cell lines, before assuming their histological subtype. 36,42 In PDX models, tumor, derived from a fresh tumor biopsy or ascites, is engrafted into immunodeficient mice. 13 Patient-derived xenograft models require propagation of the tumor into several generations of mice to create avatars for drug testing.…”

Section: Xenograft Modelsmentioning

confidence: 99%