Abstract

BackgroundOvarian cancer (OC) has the highest mortality rate in gynecologic tumors. Despite decades of continuous efforts, the survival rate of patients has not improved significantly, mostly due to drug resistance. Exosomes are hot topics in recent years. Cells can affect the biological behaviors of other cells by transferring exosomes. So far, numerous researchers have found that tumor cells can secrete exosomes which play a important role in the development of tumors. Solid tumors can promote angiogenesis. When drug resistance occurs, it seems that more blood vessels form. We suppose that exosomes derived from chemoresistant OC cells can also promote angiogenesis.ResultsWe investigate whether exosomes secreted by chemoresistant SKOV3-DDP cells (SKOV3-DDP-exo) and sensitive SKOV3 cells (SKOV3-exo) influence angiogenesis. After exosomes were extracted, exosomes were co-cultured with HUVECs. We found that SKOV3-DDP-exo and SKOV3-exo are absorbed by endothelial cells and promote the proliferation, migration, invasion and tube formation of endothelial cells. Moreover, SKOV3-DDP-exo is more powerful in angiogenesis, suggesting that parts of the components of SKOV3-DDP-exo are significantly radical. We also found that miR-130a was highly expressed in drug-resistant OC cells. Also, we found that miR-130a in SKOV3-DDP-exo is higher than SKOV3-exo. Therefore, we suggest that miR-130a in exosomes is the main cause of chemoresistant OC cells promoting angiogenesis.

Highlights

  • Ovarian cancer (OC) ranks first in the mortality rate of gynecologic cancers

  • Riches et al has revealed that breast cancer cells release 50% more exosomes than human mammary epithelial cells [19], which is consistent with OC, the number of exosomes isolated from the serum of patients is 5 times higher than that of patients with benign disease [20]

  • The above confirms that the vesicles we extracted from the cells are exosomes

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Summary

Introduction

Ovarian cancer (OC) ranks first in the mortality rate of gynecologic cancers. Because early symptoms are latent, most patients are found to be advanced. The response rate of OC to cisplatin reaches 80% and chemotherapy has significantly inhibited tumor growth, due to drug resistance, up to 70% of patients will eventually relapse, the 5-year survival rate still remains at approximately 30% [1, 2]. Exosomes are vesicles with a diameter of 30–150 nm [6], rich in lipids, proteins, RNA and DNA Various cells such as epithelial cells [7], neurons [8], T cells [9], B cells [10] can secrete exosomes. Safaei et al found that chemoresistant OC cells released 2.6 times more exosomes than parental cells previously [21]. These mechanisms of these exosomes in tumor progression is unclear. We suppose that exosomes derived from chemoresistant OC cells can promote angiogenesis

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