State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China.
Oncol Rep. 2021 Jan;45(1):278-290. doi: 10.3892/or.2020.7858. Epub 2020 Nov 18.
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.
儿童（5 岁以下）患有恶性视网膜母细胞瘤的存活率仍然很低，迫切需要阐明肿瘤发展的机制。本研究旨在揭示视网膜母细胞瘤细胞来源的外泌体（EXO）在肿瘤发展中的作用。体外数据表明，WERI-Rb1 细胞来源的 EXO 显著抑制了巨噬细胞的抗肿瘤活性，并通过增加单核细胞趋化蛋白 1（也称为 C-C 基序趋化因子配体 2）水平诱导骨髓间充质干细胞促进肿瘤生长。异种移植模型的体内数据也表明，EXO 浸润脾脏，导致白细胞和自然杀伤（NK）细胞减少。因此，与注射对照相比，注射 EXO 的肿瘤中肿瘤相关巨噬细胞的比例增加，NK 细胞的比例减少。EXO 被枯否细胞吸收，并且在肝脏中观察到更多的转移。因此，这些结果表明，源自视网膜母细胞瘤的 EXO 通过浸润微环境促进肿瘤进展。此外，可检测到 EXO 中的微小 RNA（miR），包括 miR-92a、miR-20a、miR-129a 和 miR-17，以及 C-X-C 趋化因子受体 4 和血小板反应蛋白 1，这可能是 EXO 介导的肿瘤恶化的原因。
