Extracellular vesicles (EVs) are small cellular fragments released by cells; they are surrounded by a cellular membrane and contain substances like proteins, nucleic acids, and even some organelles. They are not complete cells, and therefore they cannot replicate, but after they leave the cell of origin, they can travel and deliver their cargo to other tissues.
Recent research has demonstrated that osteosarcoma cells secrete substances that, while protected within these vesicles, can travel through the circulation to distant organs, where their content is released, pre-disposing these organs towards metastatic colonisation.
As cancers grow, certain changes occur within the immediate tumour environment (microenvironment) that influence the release and the content of extracellular vesicles (EVs). These changes are well established drivers of tumour progression and indeed metastasis.
One of these changes, is the reduced oxygen content (hypoxia) that cancer cells experience as the tumour grows.
What is this project aiming to achieve?
The main objective of this project is to investigate the role of EVs in osteosarcoma metastasis to the lungs, with a particular focus on hypoxia.
The research will provide new information on the composition of the EVs produced by osteosarcoma cells under hypoxia, and determine the effects they can trigger in lungs cells, both in vitro and in a mouse model, that can facilitate the colonisation by osteosarcoma cells and therefore lung metastasis.
How could this project improve treatment options for osteosarcoma patients?
This project has the potential to identify novel therapeutic targets for osteosarcoma metastasis, as inhibitors of the substances contained in EVs can be identified. In addition, it could open the door for utilising tumour extracellular vesicles (tEVs) as biomarkers for early metastasis.