Abstract

The poor prognosis of ovarian cancer is mainly due to metastasis, and the specific mechanism underlying ovarian cancer metastasis is not clear. Ascites-derived exosomes (ADEs) play an important role in the progression of ovarian cancer, but the mechanism is unknown. Here, we found that ADEs promoted ovarian cancer metastasis not only in vitro but also in vivo. This promotive function was based on epithelial–mesenchymal transition (EMT) of ovarian cancer cells. Bioinformatics analysis of RNA sequencing microarray data indicated that miR-6780b-5p may be the key microRNA (miRNA) in ADEs that facilitates cancer metastasis. Moreover, the expression of exosomal miR-6780b-5p correlated with tumor metastasis in ovarian cancer patients. miR-6780b-5p overexpression promoted and miR-6780b-5p downregulation suppressed EMT of ovarian cancer cells. These results suggest that ADEs transfer miR-6780b-5p to ovarian cancer cells, promoting EMT and finally facilitating ovarian cancer metastasis.

Highlights

  • Ovarian cancer has the highest mortality among gynecologic malignancies[1]

  • Ascites-derived exosomes (ADEs) enter ovarian cancer cells The four kinds of ADEs used in the subsequent experiments, which were obtained from four highgrade serous ovarian carcinoma (HGSOC) patients, including #2, #3, #7 and #27, were characterized and quantified by Transmission electron microscopy (TEM), Western blot analysis, Dynamic light scattering (DLS), NanoSight analysis (NTA) and flow cytometry

  • Western blot analysis showed that CD63 and CD9, markers of exosomes, were highly expressed in ADEs compared with cell pellets, while calnexin, a negative control for exosomes[32,33], was not present in ADEs but existed in cell pellets (Fig. 1b, Supplementary Fig. 1b)

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Summary

Introduction

Ovarian cancer has the highest mortality among gynecologic malignancies[1]. the treatment of ovarian cancer has improved in recent years, the five-year survival rate of ovarian cancer patients, which has remained at approximately 40%, has not improved significantly in the last twenty years—the survival rate in the last five years was only 41.8%2. Metastasis, nonspecific symptoms at early tumor stages and chemoresistance may be the main reasons for the poor prognosis of ovarian cancer[3,4]. Ovarian cancer patients generally manifest symptoms only after progression to an advanced stage, and only a few women are diagnosed before the tumor metastasizes to the peritoneal cavity[3]. Exosomes are extracellular vesicles with diameters of 50–140 nm that can carry small molecules, such as nucleic acids, proteins, and other bioactive molecules, to communicate between cells[8]. Exosomes secreted by tumor cells can promote tumor growth, metastasis, and angiogenesis and participate in the drug resistance of tumor cells[9,10]. High levels of exosomes have been found

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