A fluid mechanical analysis of the velocity, adhesion, and destruction of cancer cells in capillaries during metastasis.
Metastasis, a multistep process by which cancer disseminates through the body, mainly by intravascular routes, constitutes a major problem in cancer. When cancer cells are injected directly into the veins of animals, they are apparently arrested in the vascular bed of the first organ encountered and gradually released over the next 24 h. These interactions with the microvasculature are often associated in some manner with the death of many cancer cells, and are thought to contribute to the inefficiency of the metastatic process. We have made a theoretical analysis of cancer cells deformed into capillaries with respect to their intravascular velocity, adhesion to the vascular endothelium and intravascular destruction, in terms of the dynamics of the thin liquid film separating the surfaces of the blood vessels and cancer cells. Our calculations, which are based on previously reported experimental observations, indicate that the transit of cancer cells through the microvasculature is discontinuous, being interrupted by adhesions between the two. In addition, in some cases cell membrane rupture (and cell death) will occur when the critical membrane tension of the cancer cells is exceeded by the sum of their initial equilibrium membrane tension and the increased tension in the cancer cell membranes caused by friction generated as they move over the intraluminal surfaces of the capillaries. Our calculations on membrane rupture are consistent with previously unexplained observations by Sato and Suzuki relating cancer cell deformability to death on transpulmonary passage, and constitute a novel mechanism for "metastatic inefficiency" in terms of intravascular cancer cell death.
D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000502:physiology; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000503:physiopathology; D009360:Neoplastic Cells, Circulating; D012212:Rheology; D013314:Stress, Mechanical