Description
The overall objective of this project is to delineate the role of cancer-derived EVs in the progression of prostate cancer (PC) and to identify EV-enclosed small RNAs associated with cancer aggressiveness that can serve as potential therapeutic targets and/or prognostic biomarkers of prostate cancer. Project will provide opportunities for the development of novel biomarker assays for prognosis of PC and prediction of response to therapy. For the Latvian partners, this project will also provide an opportunity to gain experience in the commercialization of research results in the field of biomarkers. Partner from Norway: OUS will contribute in the project with extensive expertise and research experience. The project strengthes the expertise by mutual transfer of knowledge and collaboration between Norway and Latvia in a highly dynamic and competitive research area. Academic stuff and representatives of industry will benefit from the project results. Outcomes: Strengthened research capacity and increased application of research results: 1 internationally refereed scientific publications, 6 scientific publications co-authored by one or more reserchers from Norway and Latvia and 2 scientific publications.
Summary of project results
The main scientific objective of the project was to delineate the role of cancer-derived extracellular vesicles (EVs) in the progression of prostate cancer (PC) and to identify EV-enclosed RNA biomarkers associated with cancer aggressiveness that can serve as potential therapeutic targets and/or prognostic biomarkers of prostate cancer. Within this project, we carried out several studies focused on the characterisation of RNA, protein and lipid content of EVs released by PC cell lines or found in the blood and urine of PC patients. These studies resulted in the identification of EV-incorporated miRNAs and proteins that potentially can serve as biomarkers for the diagnosis and monitoring of PC. Furthermore, we performed a systematic comparison of PC-associated miRNA levels in whole plasma and EVs isolated from the same plasma samples. This showed that EVs provide a more consistent source of RNA than whole plasma for the analysis of some miRNA biomarkers, while, possibly due to specific sorting mechanisms, the abundance of other miRNAs in EVs is very low and they show better diagnostic performance in whole plasma. A novel model for quantifying the uptake of EVs in human immune cells using continuous and nearly physiologically relevant amounts of cancer-derived EVs was developed. Functional studies demonstrated that cancer-derived EVs are taken up by a variety of immune cells, including macrophages, T and B cells, which are found in the tumour microenvironment. In macrophages, cancer-derived EVs stimulated secretion of pro-inflammatory chemokines and cytokines, however the effect was dependent on the polarisation state of macrophages before exposure to the EVs. Results of this project are included in 10 international publications (4 published, 6 submitted) and two local scientific publications (1 published, 1 submitted) and presented at 5 international scientific conferences, meetings of the EU COST action Me-HAD and other workshops. During the visits 5 PhD students undertook various courses at University of Oslo and underwent hands-on training at the OUH laboratories thus gaining new knowledge and experience that was highly relevant for the research project and their PhD studies.
Summary of bilateral results
The bilateral cooperation support funds were used for organising a meeting of the project’s partners and covered the travel costs of the Norwegian partner for participation in the EEA/Norway grants progress meeting organised by VIAA. This allowed the project partners to share and discuss the research results, to assess the risks and problems that arose during the implementation of the project, to evaluate outcomes of the exchange visits of PhD students as well as discuss the opportunities for further collaboration. Hence, the funds contributed to achieving the project’s objectives and enhanced the prospects of further collaboration. In fact, two joint project proposals have already been submitted to ERA-NET calls. Results of this project are included in 10 international publications (4 published, 6 submitted) and two local scientific publications (1 published, 1 submitted) and presented at 5 international scientific conferences, meetings of the EU COST action Me-HAD and other workshops.