Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment

Chen,Shuilian; Chen,Xi; Qiu,Jin; Chen,Pei; Han,Xiaokun; Wu,Yihui; Zhuang,Jiejie; Yang,Meng; Wu,Chuangran; Wu,Nandan; Yang,Ying; Ge,Jian; Yu,Keming; Zhuang,Jing

doi:10.3892/or.2020.7858

Exosomes derived from retinoblastoma cells enhance tumour deterioration by infiltrating the microenvironment

Authors:
- Shuilian Chen
- Xi Chen
- Jin Qiu
- Pei Chen
- Xiaokun Han
- Yihui Wu
- Jiejie Zhuang
- Meng Yang
- Chuangran Wu
- Nandan Wu
- Ying Yang
- Jian Ge
- Keming Yu
- Jing Zhuang
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Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China
Published online on: November 18, 2020 https://doi.org/10.3892/or.2020.7858
Pages: 278-290
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The survival of young children (under 5 years of age) with malignant retinoblastoma remains poor, and clarification of the mechanism underlying tumour development is urgently needed. The present study aimed to reveal the role of exosomes (EXOs) from retinoblastoma cells in tumour development. The in vitro data indicated that EXOs derived from WERI‑Rb1 cells significantly inhibited the antitumour activity of macrophages and induced bone marrow mesenchymal stem cells to promote tumour growth via an increase in monocyte chemotactic protein 1 (also known as C‑C motif chemokine ligand 2) levels. In vivo data from a xenotransplantation model also showed that EXOs infiltrated the spleen, which induced a decrease in leukocytes and natural killer (NK) cells. Accordingly, the proportion of tumour‑associated macrophages was increased and the proportion of NK cells was decreased in tumours injected with EXOs compared with those injected with the control. EXOs were absorbed by Kupffer cells, and more metastases were observed in the liver. Thus, these results suggested that EXOs derived from retinoblastoma promoted tumour progression by infiltrating the microenvironment. Moreover, microRNAs (miRs), including miR‑92a, miR‑20a, miR‑129a and miR‑17, and C‑X‑C chemokine receptor type 4 and thrombospondin‑1 were detectable in EXOs, which might account for EXO‑mediated tumour deterioration.

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