Cancer-cell traffic in the liver. III Lethal deformation of B16 melanoma cells in liver sinusoids.
It has previously been shown that most of the B16F10 melanoma cells delivered to the mouse liver via the portal vein are rapidly killed in periportal zone 1 of the sinusoids. Few intact viable cells reach pericentral zone 3 of the sinusoids and of these, only a very small proportion leave the liver to colonize the lungs. The hypothesis has been advanced that one non-exclusive, potential mechanism for cancer-cell destruction in the liver is a result of the deformation of cancer cells when they enter vessels of smaller diameter than themselves. Where entry is associated with change in shape from spheroid to cylindrical, a mandatory increase in cancer-cell surface area occurs, which is first apparent and utilizes surface membrane excess (rugosity). If this increase is insufficient, a real increase occurs which, if in excess of approximately 4%, results in lethal surface membrane rupture. This hypothesis predicts that, under these circumstances, cancer-cell resistance to mechanical trauma is favored by small diameter and utilizable surface membrane excess. To test this hypothesis, the traffic of melanoma cells in the liver following portal-vein injection has been observed by confocal microscopy and image reconstruction. In accordance with the hypothesis, non-disrupted cells within the sinusoids have a smaller mean diameter than that of the original inoculum, and show evidence of utilization of surface membrane excess. The results indicate that deformation-associated trauma, suffered by cancer cells on entry and residence in the microvasculature, may well be an important factor contributing to metastatic inefficiency.
Barbera-Guillem
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Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, NY.
Weiss
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D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation