Computational Investigation of Role of Platelets In Cancer Metastasis

Abstract

Recent studies suggest that platelets have a significant role in improving the survival 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, activated platelets adhere to circulating cancer cells in the bloodstream and exacerbate the metastasis process in different ways. We hypothesize that: (1) platelets can protect circulating tumor cells from being destroyed 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 destroying 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 that increases the permeability of vessels. These hypotheses have been stated several times in the literature, but the underlying mechanism of the platelet-cancer cell is still a mystery. Hence, in order to test these hypotheses and to find new therapeutic methods to reduce metastasis outcomes, we investigated the interactions between circulating tumor cells, blood flow, and platelets via computational modelling at the cellular scale. We used the Lattice Boltzmann method to simulate the plasma flow, the Discrete Element Method to model the deformation of the cells, and the Immersed Boundary Method to allow interactions between the plasma flow and deformable cells. We defined cell-cell and cell-vessel wall adhesion forces based on a stochastic adhesion model. 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.