Mechanism of mechanical trauma to Ehrlich ascites tumor cells in vitro and its relationship to rapid intravascular death during metastasis.

Many, if not most, of the cancer cells arrested in the microvasculature during metastasis appear to be rapidly killed by mechanical trauma, associated with shape-transitions, which require increases in cell surface area. The hypothesis has been advanced that such increases in surface area occur in 2 phases: First, there is an apparent increase due to surface unfolding, which is reversible and non-lethal. Second, there is a true increase, during which cell surface membranes are stretched, with an increase in membrane tension. When tension exceeds a critical level, the surface membranes rupture and this irreversible change is lethal. In the present study, cell surface area has been incrementally increased by a hypotonic environment. Down to approximately 70 mM/kg, a reversible, non-lethal increase in cell volume was observed, associated with electron microscopic evidence of unfolding. At and below 70 mM/kg, irreversible, lethal changes occurred, associated with increased susceptibility to the mechanical trauma associated with membrane-filtration. These observations are consistent with the hypothesis in question.