Fluid Mechanics Webinar Series

Tumor cell metastasis: Modeling the long and treacherous journey in the circulation and escape at the metastatic site

Roger D.Camm, Massachusetts Institute of Technology

More than 90% of the mortality due to cancer is attributable to metastatic disease, yet we have at best a limited understanding of the barriers faced by a tumor cell as it is convected by blood flow from the primary tumor to the remote metastatic site. Our group has focused on developing physical models that address many of these barriers including: 1) arrest in the remote microcirculation either by adhesion or trapping, 2) survival while still inside the vessel against the stresses of fluid flow and immune cell attack, and 3) transmigration across the endothelial monolayer. The stresses experienced by the tumor cell and the respective roles of tumor cell stiffness and adhesion, endothelial permissiveness or resistance to invasion, and nuclear deformations leading to changes in cellular phenotype are all factors that combine to determine the outcome of metastatic seeding: death, proliferation, or dormancy with the potential for later transition to a proliferative state. In this presentation I will track the steps of the metastatic cascade and demonstrate how physical and computational models can shed light on these rate limiting processes.