A Computer Model for Simulation of the Influence of the Cell-Platelet Interaction on the Metastasis of the Circulating Tumor Cells (CTC)

Within the multi-stage process of metastasis, there is a separation of cancer cells, so-called circulating tumor cells (CTCs), from the primary tumor, and their journey to the target organ where they remain. On the way to the target organs, CTCs pass through the circulatory system where they interact with host cells. Recent studies have suggested that platelets have a crucial role in enhancing the survival of circulating tumor cells in the bloodstream and aggravating cancer metastasis. The main physiological function of platelets is to create a blood clot by binding to the injured sites on the vessel to stop bleeding. However, in cancer patients, activated platelets adhere to circulating tumor cells and exacerbate metastatic spreading. To examine the biophysical conditions needed for CTC arrest, we used a custombuilt viscoelastic solid-fluid 2D computational model that enables the calculation of the limiting cases for which CTC will get stacked into the capillary by the influence of platelets. Two representative examples were developed a) cell in narrowing with platelets and b) cell in wide capillary with platelets attached to the cell. By exploring the parameter space, a relationship between the capillary blood pressure gradient and the CTC mechanical properties (size and stiffness) and platelet size, is determined. Based on the results obtained using the presented software and platform, it can be concluded that the platform can be a useful tool in studying biological conditions for CTC arrest, studying the mechanism of interaction between cells and platelets, as well as predicting disease progression.