Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer.

Autor: Albino D; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Falcione M; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Uboldi V; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Temilola DO; International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa and Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Sandrini G; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Merulla J; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Civenni G; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Kokanovic A; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Stürchler A; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Shinde D; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Garofalo M; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padova, Italy., Mestre RP; Medical Oncology, Oncology Institute of Southern Switzerland, 6500, Bellinzona, Switzerland., Constâncio V; Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal., Wium M; International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa and Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Burrello J; Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, USI, Lugano, Switzerland., Baranzini N; Department of Biotechnology and Life Science, Università degli Studi dell'Insubria, Varese, Italy., Grimaldi A; Department of Biotechnology and Life Science, Università degli Studi dell'Insubria, Varese, Italy., Theurillat JP; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Bossi D; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Barile L; Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, USI, Lugano, Switzerland., Henrique RM; Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.; Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Porto, Portugal., Jeronimo C; Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.; Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), Porto, Portugal., Zerbini LF; International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa and Integrative Biomedical Sciences Division, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Catapano CV; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland., Carbone GM; Institute of Oncology Research (IOR), Università della Svizzera Italiana (USI), 6500, Bellinzona, Switzerland. pina.carbone@ior.usi.ch.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Jan 26; Vol. 4 (1), pp. 119. Date of Electronic Publication: 2021 Jan 26.
DOI: 10.1038/s42003-020-01642-5
Abstrakt: 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 (LNCaP abl ), transgenic mice (Pb-Cre4;Pten flox/flox ;Rosa26 ERG/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.
Databáze: MEDLINE
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