Cancer Cell Migration

Cancer is the attributed cause of death in one in four cases in the United States and metastasis, a complex multistep process leading to the spread of tumors, is responsible for more than 90% of these deaths. However, predicting the location of these secondary tumor sites remains an elusive goal. Development of a precise understanding of cell movement through the vascular system and the likelihood of penetration of the vessel wall is critical to achieving the ultimate goal of reliably predicting the vascular regions most likely to incur secondary tumor sites on a per-patient basis. Predictable patterns will have a 3-fold benefit: (1) supporting a more directed search for metastases in selected sites when the stage of cancer is being determined; (2) enabling the prediction of the primary site for patients with metastatic disease of unknown origin; (3) informing next-generation nanotechnologies that target cancer cells in the blood stream.

red blood cells

Our interest in cancer cell migration stems from our long-standing interest in understanding fluid-structure interactions and their subsequent impact on disease localization. The lattice Boltzmann method (LBM) is a mesoscopic model of fluid dynamics that can efficiently simulate flow in complex geometries. We use the LBM framework as the basis for HARVEY, our large-scale parallel fluid dynamics application. To study the movement of rare cancer cells through the vasculature and their interaction with other bodies suspended in the flow such as red blood cells, white blood cells, or platelets, we use the Immersed Boundary Method (IBM) to describe the cells. Using such multiscale modeling to account for factors such as residence times and collision rates, we are investigating the role of flow patterns and cellular interactions as prognostic indicators for cell adhesion and formation of secondary tumor sites. Below, we show an example from a recent publication studying the movement of a compound capsule through a constricted microchannel. This research lays the groundwork for future studies to investigate the influence that material properties of cancer cells have on their transport through the circulatory system.

shapes during constriction passage
Shapes during constriction passage (from left to right): entering, transition, existing, and returning to the full channel, for simple (top) and compound (bottom) capsules. Colored by membrane velocity in m/s. Gounley, J., Draeger, E.W., and Randles, A. "Numerical simulation of a compound capsule in a constricted microchannel." Elsevier Procedia Computer Science, International Conference on Computational Science. (2017).