The differential resistance of B16 wild-type and F10 cells to mechanical trauma in vitro.
Following intravenous injection of B16 melanoma cells into mice, more than 99.9% of the cells are killed by a combination of rapid and slow processes: however, the F10 line of B16 mouse melanoma cells produces approximately 10 times as many pulmonary colonies as wild-type cells. We have attempted to determine the role of one rapid cancer cell-killing process, namely deformation-driven, loss of surface membrane integrity of the type occurring in capillaries, by the use of an in vitro model in which cells are filtered through 8-microns pores in polycarbonate membranes. In accord with in vivo observations, more wild-type than F10 cells were killed by filtration in vitro. The hypothesis that resistance to mechanical trauma of this type is enhanced by a small cell diameter and a high degree of surface rugosity is supported by measurements of these parameters on viable cells and electron micrographs. Differential resistance in these cells is associated to a major extent with a high degree of utilizable surface membrane excess, and to a minor extent with the smaller mean diameter of the F10 cells. Calculations, which are in accord with previous in vivo observations, indicate that most of the cells delivered to the capillary beds of target organs during hematogenous metastasis can be destroyed by rapid mechanical trauma, which is therefore implicated as one of a number of major contributors to metastatic inefficiency.
Weiss
L
L
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Elkin
G
G
Barbera-Guillem
E
E
D005374:Filtration; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000473:pathology* / Q000648:ultrastructure; D009362:Neoplasm Metastasis / Q000473:pathology*; D013314:Stress, Mechanical