P20. Extracellular vesicle–mediated delivery of miR-210 drives angiogenesis in retroperitoneal sarcomas

Retroperitoneal soft-tissue sarcomas (RSTS) are rare and heterogeneous tumors. Angiogenesis, a fundamental hallmark of cancer, is essential for tumor progression and metastasis. Extracellular vesicles (EVs) serve as key mediators of intercellular communication and can modulate angiogenesis through the transfer of molecular cargo, including miRNAs. In this study, we explore the pro-angiogenic role of miR-210 carried by RSTS-derived EVs, using an innovative multicellular 3D spheroid model.


Methods: Extracellular vesicles (EVs) were isolated from human liposarcoma, fibrosarcoma, and leiomyosarcoma cell cultures and used to stimulate endothelial cells (ECs). Functional assays were performed to assess EC proliferation, migration, and invasion, while angiogenesis was evaluated using in vitro Matrigel tube formation and in vivo plug assays. The expression of angiogenesis-associated microRNAs (miR-130a and miR-210) was quantified in both RSTS-derived EVs and in stimulated ECs by qRT-PCR. Finally, multicellular 3D spheroids composed of ECs and RSTS cells were employed to specifically investigate the role of EV-derived miR-210 in angiogenesis.


Results:

EVs derived from all three RSTS cell lines markedly enhanced EC proliferation, migration, and invasion. They also promoted angiogenesis, as demonstrated by increased tube formation in vitro and elevated CD31-positive vessel density in plug assay sections in vivo. In addition, ECs exposed to RSTS-derived EVs showed upregulation of miR-130a and miR-210. Multicellular spheroids composed of ECs and RSTS cells were successfully generated, and treatment with EVs overexpressing miR-210 led to an increased number of ECs within the spheroids.


Conclusions:

RSTS-derived EVs promote angiogenesis by enhancing endothelial cell functions and transferring pro-angiogenic miRNAs, particularly miR-210. These findings suggest that EV-mediated signaling contributes to sarcoma progression through modulation of the tumor microenvironment.