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. 2021 Jan 7;14(1):7.
doi: 10.1186/s13048-020-00758-w.

Exosomes secreted by chemoresistant ovarian cancer cells promote angiogenesis

Zhang Li  1   2 , Wang Yan-Qing  1 , Yang Xiao  1 , Liu Shi-Yi  1 , Yuan Meng-Qin  1 , Xian Shu  1 , Yang Dong-Yong  1 , Zheng Ya-Jing  1 , Cheng Yan-Xiang  3
Affiliations

Exosomes secreted by chemoresistant ovarian cancer cells promote angiogenesis

Zhang Li et al. J Ovarian Res. .

Abstract

Background: Ovarian 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.

Results: We 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.

Keywords: Angiogenesis; Drug resistance; Exosomes; Ovarian cancer; miR-130a.

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Conflict of interest statement

All authors state that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Characterization of exosomes derived from cell lines IOSE80, SKOV3, and SKOV3-DDP. a Transmission electron microscopy images of IOSE80-exo, SKOV3-exo, and SKOV3-DDP-exo. Scale bars = 100 nm. b Size distribution (nm) of IOSE80-exo, SKOV3-exo, and SKOV3-DDP-exo were determined by Software ZetaView. c Western blot analysis of surface markers HSP70, CD9, and CD63 in IOSE80-exo, SKOV3-exo, and SKOV3-DDP-exo
Fig. 2
Fig. 2
a The internalization of IOSE80-exo, SKOV3-exo and SKOV3-DDP-exo (PKH26-labeled, red fluorescence) by HUVECs (Hoechst 33342-labeled, green fluorescence) was examined by confocal laser scanning microscopy. b Proliferation of HUVECs co-cultured with SKOV3-exo, or SKOV3-DDP-exo was measured by CCK-8, cells treated with PBS were served as the control. c-d Migration of HUVECs co-cultured with SKOV3-exo, or SKOV3-DDP-exo was measured by scratch assays. Cells treated with PBS were served as the control. e-f Invasion of HUVECs co-cultured with SKOV3-exo, or SKOV3-DDP-exo was measured by transwell assay, cells treated with PBS were served as the control. g Capillary-like tubes of HUVECs co-cultured with SKOV3-exo, or SKOV3-DDP-exo were measured by tube formation experiment, cells treated with PBS were served as the control. *p < .05, **p < .01, ***p < .001
Fig. 3
Fig. 3
Expression of miR-130a in exosomes derived from SKOV3 and SKOV3-DDP cells
See this image and copyright information in PMC

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