Investigating dynamical deformations of tumor cells in circulation: predictions from a theoretical model

摘要

It is inevitable for tumor cells to deal with various mechanical forces in order to move from primary to metastatic sites. In particular, the circulating tumor cells that have detached from the primary tumor and entered into the bloodstream need to survive in a completely new microenvironment. They must withstand hemodynamic forces and overcome the effects of fluid shear before they can leave the vascular system (extravasate) to establish new metastatic foci. One of the hypotheses of the tumor cell extravasation process is based on the so called “adhesion cascade” that was formulated and observed in the context of leukocytes circulating in the vascular system. During this process, the cell needs to switch between various locomotion strategies, from floating with the blood stream, to rolling on the endothelial wall, to tumor cell arrest and crawling, and finally tumor cell transmigration through the endothelial layer. The goal of this project is to use computational mechanical modeling to investigate the fundamental biophysical parameters of tumor cells in circulation. As a first step to build a robust in silico model, we consider a single cell exposed to the blood flow. We examine parameters related to structure of the actin network, cell nucleus and adhesion links between the tumor and endothelial cells that allow for successful transition between different transport modes of the adhesion cascade.