Margination and adhesion dynamics of tumor cells in a real microvascular network

Author summary Cancer is one of leading causes of death in the world, but unfortunately, the mechanism of tumor metastasis remains unclear so far. Intuitively, the tumor metastasis starts from a tumor cell migrating towards the vessel wall (namely margination), then adhering to the vessel wall (namely adhesion), and finally extravasating from where it adheres onto. Hence, it is important to investigate the margination and adhesion of tumor cells for understanding the tumor metastasis. We implemented a three-dimensional simulation to directly reproduce these two processes at a cellular scale, where the dynamic behaviors, such as deformation, aggregation and adhesion, of a lot of cells in a very complex microvascular network are taken into account. The results suggest that the tumor cells may be prone to adhere at the microvascular bifurcations with low shear rate and moderate hematocrit, because of a high wall-directed force from the surrounding RBCs. This implies that the tumor may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate. Our work may provide new insights into the cancer pathophysiology and its diagnosis and therapy. In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate.

Automated summary

The study reveals that tumor cells are more likely to adhere at microvascular bifurcations with low shear rate and moderate hematocrit, increasing the probability of extravasation. It provides new insights into cancer pathophysiology and suggests potential implications for diagnosis and therapy.