The study by Albino et al. is published in Communications Biology and is available at https://doi.org/10.1038/s42003-020-01642-5.
The work is a collaborative effort involving many researchers at the IOR and at research centers in Ticino (IOSI, EOC), Italy (University of Padova and University of Varese), Portugal (IPO Porto), and South Africa (ICGEB).
The team has evaluated the cargo of circulating plasma exosomes released by primary and metastatic tumors and found that the level of a microRNA, miR-424, was increased in exosomes from patients with the more aggressive tumors. miR-424 is a potent oncogenic microRNA and its transfer via circulating exosomes promotes tumor-initiating and stem cell properties in the receiving cells in the immediate microenvironment and, through the blood circulation, at distant metastatic sites. The study provides a comprehensive analysis of the consequences of the release of circulating plasma exosomes in cancer patients, demonstrating the important role of this phenomenon in tumor progression and recurrence. These results may lead to novel approaches for diagnosing, monitoring and treatment of prostate cancer.
Circulating extracellular vesicles release oncogenicmiR-424 in experimental models and patients with aggressive prostate cancer.
Domenico Albino, Martina Falcione, Valeria Uboldi, Dada Oluwaseyi Temilola, Giada Sandrini, Jessica Merulla, Gianluca Civenni, Aleksandra Kokanovic, Alessandra Stürchler, Dheeraj Shinde, Mariangela Garofalo, Ricardo Pereira Mestre, Vera Constâncio, Martha Wium, Jacopo Burrello, Nicolò Baranzini, Annalisa Grimaldi, Jean-Philippe Theurillat, Daniela Bossi, Lucio Barile, Rui M. Henrique, Carmen Jeronimo, Luiz Fernando Zerbini, Carlo V. Catapano and Giuseppina M. Carbone.
COMMUNICATIONS BIOLOGY (2021)4:119. https://doi.org/10.1038/s42003-020-01642-5.
Extracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH. Release of miR-424 in small EVs was enhanced in cell lines (LNCaPabl), transgenic mice (Pb-Cre4;Ptenflox/flox;Rosa26ERG/ERG) and patient-derived xenograft (PDX) models of aggressive disease. EVs containing miR-424 promoted stem-like traits and tumor-initiating properties in normal prostate epithelial cells while enhanced tumorigenesis in transformed prostate epithelial cells. Intravenous administration of miR-424 positive EVs to mice, mimicking blood circulation, promoted miR-424 transfer and tumor growth in xenograft models. Circulating miR-424 positive EVs from patients with aggressive primary and metastatic tumors induced stem-like features when supplemented to prostate epithelial cells. This study establishes that EVs-mediated transfer of miR-424 across heterogeneous cell populations is an important mechanism of tumor self-sustenance, disease recurrence and progression. These findings might indicate novel approaches for the management and therapy of prostate cancer.