Luca Primo, Ph.D.
University of Torino Medical School
Molecular mechanisms that differentiate invasive cancer cells from their non-motile counterparts, and the relationship between tumor and non-tumor cells during cell migration.
Cancer cells spread from the initial site of tumor growth acquiring an invasive phenotype characterized by both the loss of cell-cell interactions and increased cell motility. Cells undergoing this epithelial to mesenchymal transition are then able to move and spread throughout the entire body as isolated and highly motile cells. Recent evidence shows that tumor cells also move as groups both in normal development and in cancer models, in a process named “collective migration”. Even vascular endothelial cells collectively migrate into tumor mass forming new vessels in a process called “tumor angiogenesis”.
We are developing new three-dimensional (3D) culture systems that in combination with conventional cell biology approaches, allow the study of collective and directional cell migration. A new model for in vitro tumor angiogenesis studies has been described and cell spheroid cultures from breast and prostate cell lines have been developed. With these three-dimensional models we have been able to discover new mechanisms of PI3K regulation of collective migration and the role of the endothelial podosome in tumor angiogenesis.
Conclusions and perspectives:
We believe that spheroids/organoids 3D culture from cells and tissues could overcome limitations of established cell lines, such as adaptation to 2D growth, providing better models to study collective migration, epithelial-to mesenchymal transition and tumor vascularization, and the identification of molecular mechanisms involved in these processes. Moreover, we are establishing 3D cell cultures from patient-derived xenograft (PDX) of colon cancer with a high percentage of in vitro engraftment. By combining our know-how in 3D cultures with the PDX platform developed in the Institute, we will implement an unprecedented in vitro platform for genetic functional and drug screening purposes.
Puliafito Alberto, PhD
Laura Di Blasio, PhD