期刊
CLINICAL SCIENCE
卷 132, 期 18, 页码 2029-2044出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20180425
关键词
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资金
- Lions Medical Research Foundation [606833]
- Ovarian Cancer Research Foundation (OCRF) [020780]
- UQ-Ochsner Seed Fund for Collaborative Research [610193]
- University of Queensland
- Faculty of Medicine M+BS Emerging Leaders Medical Research Grant
- Fondo Nacional de Desarrollo Cientifico y Tecnologico [FONDECYT 1170809]
- Ovarian Cancer Research Foundation [2018001167]
- Research Training Program Scholarship from the University of Queensland - Commonwealth Government of Australia
Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In the present study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and buoyant density centrifugation and characterised using nanoparticle tracking analysis (NTA), Western blot, and EM. Exosome secretion was positively correlated with invasiveness of releasing cells. Proteomic analyses identified common and unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology analyses revealing that these exosomes are involved in the regulation of cell migration. Since the tumour microenvironment contains multiple cell types, including MSCs and ECs, we examined the effect of these exosomes on MSC and EC migration. Exosomes promoted MSC and EC migration in a time-and concentration-dependent manner. The effect of exosomes isolated from SKOV-3 on cell migration was significantly higher compared with exosomes from OVCAR-3. Thus, we suggest that exosomes from ovarian cancer cells contain a specific set of proteins that are representative of its cell of origin and the invasive capacity.
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