Recent studies suggest that platelets have a significant role in facilitating the generation of circulating tumor cells and aggravating cancer metastasis. The main function of platelets, as a blood constituent, is to bind to the sites of the damaged vessels and stop bleeding. However, in cancer patients, platelets also adhere to circulating cancer cells in the bloodstream and exacerbate the metastasis process in different ways. Experimental studies in patients showed a relationship between elevated platelet count and higher number of metastatic tumors. Furthermore, platelet count per unit volume is associated with the stages of cancer. We hypothesize that: (1) platelets can protect circulating tumor cells from destroying by the blood flow due to large deformations and high shear stress; (2) platelets can form a protective layer around the circulating tumor cells that prevent the white blood cells from recognizing and killing circulating tumor cells, increasing the survival rate of circulating tumor cells; (3) platelets enhance the extravasation of circulating tumor cells by increasing the number of adhesion bonds to the vessel wall and by secreting vascular endothelial growth factor which increases the permeability of vessels. Hence, in order to test these hypotheses and to find new therapeutic methods to reduce metastasis outcome, we investigated the interactions between circulating tumor cells, blood flow and platelets via computational modelling at the cellular scale. Monitoring the alteration of platelet count can also provide us a useful biomarker to determine the stage of cancer. We used the lattice Boltzmann method to simulate the plasma flow, discrete element method to model the deformation of the cells, and immersed boundary method to allow interactions between the plasma flow and deforming cells. We defined cell-cell and cell-vessel wall adhesion forces based on a stochastic adhesion model. We will validate our computational model against experimental results from the literature. Our highly detailed computational model helps us to understand and explain these phenomena and provides an effective tool to design and test new potential therapeutic methods based on platelet regulation.
*snapshot of computational domain showing the firm adhesion of a circulating tumor cell with is modulated by platelets (in green)