Oncotarget

Research Papers:

Malignant ascites: a source of therapeutic protein against ovarian cancer?

Pascale Ribaux, Aurore Britan, Gabriele Thumann, Florence Delie, Patrick Petignat and Marie Cohen _

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Oncotarget. 2019; 10:5894-5905. https://doi.org/10.18632/oncotarget.27185

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Abstract

Pascale Ribaux1,2, Aurore Britan1, Gabriele Thumann3,4, Florence Delie5, Patrick Petignat1 and Marie Cohen1,2

1 Department of Pediatrics, Gynaecology and Obstetrics, Faculty of Medicine, Geneva 1206, Switzerland

2 Translational Research Center in Oncohaematology, Faculty of Medicine, Geneva 1206, Switzerland

3 Experimental Ophthalmology, University of Geneva, Geneva 1205, Switzerland

4 Department of Ophthalmology, University Hospitals of Geneva, Geneva 1205, Switzerland

5 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva 1205, Switzerland

Correspondence to:

Marie Cohen,email: [email protected]

Keywords: ascites; PEDF; sleeping beauty transposon; ovarian cancer; tumor development

Received: June 12, 2019     Accepted: August 12, 2019     Published: October 15, 2019

ABSTRACT

Ovarian cancer is the fifth leading cause of cancer-related death in the world. Some ovarian cancer patients present large amount of ascites at the time of diagnosis which may play an active role in tumor development. In earlier studies, we demonstrated that the acellular fraction of ascites can induce apoptosis of ovarian cancer cells. The current study identifies pigment epithelium derived factor (PEDF) as the molecule responsible for the apoptotic effect of ascites and evaluates the Sleeping Beauty transposon (SBT) system as a new tool for PEDF gene therapy against ovarian cancer. We utilize gel filtration, mass spectrometry, affinity column, cell viability assay, tumor development on chick chorioallantoic membrane and molecular biology techniques for these purposes. PEDF was thus identified as the agent responsible for the effects of ascites on ovarian cancer cell viability and tumor growth. Interestingly, the PEDF expression is decreased in ovarian cancer cells compared to healthy ovarian cells. However, the level of PEDF is higher in ascites than in serum of ovarian cancer patients suggesting that cells present in the tumor environment are able to secrete PEDF. We then used the SBT system to stably induce PEDF expression in ovarian cancer cells. The overexpression of PEDF significantly reduced the tumor growth derived from these cells. In conclusion, the results presented here establish that PEDF is a therapeutic target and that PEDF from ascites or SBT could be utilized as a therapeutic strategy for the treatment of ovarian cancer.


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