Cancer Tissue Engineering: development of new 3D models and technologies to support cancer research

The activity of research of this thesis focuses on the relevance that appropriate models reproducing the in vivo tumor microenvironment are essential for improving cancer biology knowledge and for testing new anticancer compounds. Animal models are proven not to be entirely compatible with the human system, and the success rates between animal and human studies are still unsatisfactory. On the other hand, 2D cell cultures fail to reproduce some aspects of tumor system. These limitations have a significant weight especially during the screening of novel antitumor drugs, as it was demonstrated that cells are less sensitive to treatments when in contact with their microenvironment. To obtain the same tumor cell inhibition levels observed in vivo, the culture environment has to reflect the 3D natural environment. Natural or synthetic hydrogels reported successful outcomes in mimicking ECM environment. During this PhD, I developed different gel-based scaffolds to be use as substrates for the culture of breast cancer cells. In detail, I developed different gels for low and highly aggressive cancer cell lines (i.e. MCF-7 and MDA-MB-231), obtaining significant results as regards the reproduction of key features normally present into the in vivo environment. Considering the importance of the metastasis process in breast cancer evolution, I then focused on a new set-up for the observation of cancer cell motility and invasion. In particular, I combined a bioreactor-based bioengineering approach with single cell analysis of Circulating Tumor Cells (CTCs). This part of work was carried out at the Dipartiment of Biomedicine of the University of Basel (CH) that, among its equipment, has a cell celector machine for single cell analysis. At the end of this work, I provided a proof-of-concept that the approach can work, as well as evidence that the cells can be extracted from the device and used for molecular analysis.