Next generation of cancer models for improved predictivity in drug development – 3D colorectal cell growth with the use of supporting spider silk
About the project
Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide, and the prognosis for patients with metastatic CRC is poor. Common methods to culture cells in vitro today are monolayer 2D cell cultures, which are not accurately representing the interactions in vivo between the CRC cells and other components in the 3D cell environment. The extracellular matrix (ECM) includes cell types such as immune cells, cancer-associated fibroblasts (CAFs) and stromal cells. The development of safe and effective drugs is currently hampered by the poor predictive power of existing preclinical animal models and can lead to the failure of drug candidates in human trials. It is necessary to provide physiologically relevant models, so that the results are representative.
The ECM plays a very important role for cells grown in 3D cell models, and increase the resemblance of the in vivo conditions including cell morphology, cell polarity, protein-, biomarker- and gene expression. Laminins in the ECM are involved in many stages of cancer progression, and expression of laminin genes has prognostic value in various types of cancer, including CRC. Laminin-functionalized recombinant spider silk (BioSilk) will be used to build up, develop optimized protocols and evaluate the advanced and complex 3D CRC cell culture models in this project. We will compare treatment of BioSilk-cultured CRC in 3D with monolayer 2D cells with and without Biolaminin. To the 3D CRC cell culture models, supporting cells will be added and the result will be evaluated.
Two life science companies and in total four academic institutions will with joint expertise develop protocols, perform advanced 3D CRC cell culture models, use novel treatment for the CRC cells and disseminate the results to a wide audience. This includes research groups, medical doctors and the society. The results of the study will provide useful tools for research groups culturing cancer cells in vitro, as well as for clinicians and the drug development industry, since our aim is that the model will be offered to others, and used.