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Distant spreading of primary lesions is modulated by the vascular dynamics ofcirculating tumor cells (CTCs) and their ability to establish metastaticniches. While the mechanisms regulating CTC homing in specific tissues are yetto be elucidated, it is well documented that CTCs possess different size,biological properties and deformability. A computational model is presented topredict the vascular transport and adhesion of CTCs in whole blood. ALattice-Boltzmann method, which is employed to solve the Navier-Stokes equationfor the plasma flow, is coupled with an Immersed Boundary Method. The vasculardynamics of a CTC is assessed in large and small microcapillaries. The CTCshear modulus k ctc is varied returning CTCs that are stiffer, softer andequally deformable as compared to RBCs. In large microcapillaries, soft CTCsbehave similarly to RBCs and move away from the vessel walls; whereas rigidCTCs are pushed laterally by the fast moving RBCs and interact with the vesselwalls. Three adhesion behaviors are observed, firm adhesion, rolling andcrawling over the vessel walls, depending on the CTC stiffness. On thecontrary, in small microcapillaries, rigid CTCs are pushed downstream by acompact train of RBCs and cannot establish any firm interaction with the vesselwalls; whereas soft CTCs are squeezed between the vessel wall and the RBC trainand rapidly establish firm adhesion. These findings document the relevance ofcell deformability in CTC vascular adhesion and provide insights on themechanisms regulating metastasis formation in different vascular districts.

Unraveling the vascular fate of deformable circulating tumor cells via a hierarchical computational model