Measuring metastasis in a miniature multi-organ system
This project is aimed to build a fully human-based cell culture system to assess invasion of circulating tumour cells into healthy micro-tissues. To achieve this, the unique biological tools of the Dept of Urology of the Erasmus MC are connected to the multi-tissue 3D organoid microfluidic system developed by InSphero, Schlieren, Switzerland.
New therapies for metastasised cancer are being tested in (animal) models of primary tumors that are not representative for metastatic disease. However, the preferential invasion and colonisation of circulating tumour cells (CTCs) in specific organs is likely impacted by the applied therapy. Hence, it is highly relevant to apply early drug screens in models that reflect clinically relevant metastatic sites.
Now, in this project, a fully human-based 3D culture system will be build that allows to study metastatic invasion of CTCs into different healthy micro-tissues. For this, (fluorescently-tagged) metastatic prostate cancer cells mimicking CTCs will be used, to flow along micro-tissues of human healthy (liver) tissue. This new bioassay will allow to assess invasive potential in a biologically relevant system and identify tumour cell and tissue factors that determine cell invasion into healthy tissues, which may guide metastasis-targeted drug development and support non-animal drug testing.
At the end of the project, a bioassay for metastatic invasion of (prostate) cancer cells into human healthy (liver) tissue will be delivered that can be applied in compound screens and drug testing. Initially being developed on the basis of prostate cancer cells with proven metastatic potential towards liver, the platform will also be tested for its applicability in other cancer types with (liver) metastatic disease, such as breast cancer and bladder cancer. Finally, it is expected that the test system will contribute to the reduction of animal use and may (at least in part) replace animal experimentation during drug development.
