Effects Of Micro Flow On Adhesion And Migration Of Tumor Cells

The microenvironment of tumor metastasis can be divided into two different types:One is situated in such blood flows within venules and the other is in extracellular matrix(ECM).After finishing adhesion and extravasation to the blood vessel,tumor cells invade to surrounding tissue and metastasis to distant organs.Better understanding of mechanism of the tumor migration is important to cancer diagnosis and treatment.According to the published experimental data,we establish a biomechanical model to study the two issues of tumor metastasis:1)Interaction between a circulating tumor cell and a leukocyte in blood vessel.2)Migration of a cancer cell through 3D ECM.Previous study shows the adhesion efficiency of circulating tumor cells can be double promoted since leukocytes exist.The hydrodynamic environment has an important influence on the tumor adhesion in blood shear flow.In this dissertation,a computational software coupled with a quasi-steady description is exploited to investigate the micro environment of a tumor cell approaching the wall.The final adhesion is determined by biomechanical cues during the cell migration progress.On the condition of shear rate 50 s^-1,the tumor cell rolls along the surface of the leukocyte during entire progress.The contact time of the tumor cell and leukocyte is doubled influenced by the biochemical bond.On the condition of shear rate 200 s^-1,the tumor cell detaches from the leukocyte at a moment.The contact time is prolonged by 58.6%influenced by the biochemical bond,which facilitates tumor cell adhesion to the leukocyte.When the shear rate is high and the number of receptors on cell surface is small,tumor cell adheres to the leukocyte.On the contrary,tumor cell cannot be adhered when the shear rate is low as well as the number of receptors on cell surface is large.Criterion of tumor cell adhesion is obtained with regard to shear rate and the number of receptors.ECM is the primary component of human tissues and the main fraction of ECM is collagen fiber and interstitial flow.Tumor metastasizes through surrounding tissues is directly related to the properties of ECM,such as interstitial flow,distribution of chemokines,collagen fiber alignment and stiffness of ECM.In this paper,the realignment of collagen fiber is studied from the perspective of mechanics.According to the analysis of a slender body in low-Reynolds-number flow proposed by Cox,we deduce the hydrodynamic force on the cylindrical fiber as well as the flow speed effect on the fiber alignment.Factors such as cell migration speed,ECM alignment and stiffness are integrated into the ECM resistance model.Ultimately,the tumor migration model is established based on the binding force,chemotaxis and balancing equation.Based on this model,we investigate the flow versus fiber reconstitution,flow versus fiber alignment and flow versus ECM stiffness.Matlab program and computational software are utilized to simulate cancer cell migration.Comparing the simulation and experiment,we claim 1)ECM realignment caused by interstitial flow facilitates tumor directional migration.2)Interstitial flow and parallel aligned ECM have synergistical effect on cell migration.Allometric function is found between the displacement and flow speed.3)Interstitial flow and ECM stiffness have synergistical effect on cell migration.4)Shear stress enhances the binding strength.The asymmetric shear stress at upstream and downstream of cell leads to cell migrating against flow.