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

Oncol Rep. 2021 Jan;45(1):278-290. doi: 10.3892/or.2020.7858. Epub 2020 Nov 18.

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.

Keywords: exosomes; retinoblastoma; macrophages; tumour microenvironment; metastasis.

MeSH terms

  • Animals
  • Carcinogenesis / immunology*
  • Carcinogenesis / pathology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Chemokine CCL2 / metabolism
  • Child, Preschool
  • Coculture Techniques
  • Exosomes / immunology*
  • Exosomes / metabolism
  • Female
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mesenchymal Stem Cells
  • Mice
  • MicroRNAs / metabolism
  • Primary Cell Culture
  • Retinoblastoma / immunology*
  • Retinoblastoma / pathology
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • MicroRNAs