Cancer-cell traffic in the liver. II. Arrest, transit and death of B16F10 and M5076 cells in the sinusoids.

Abstract

Fluorescent probes were used to detect BUdR-labelled B16F10 and M5076 cancer cells delivered to the livers of mice via intrasplenic injection. In liver sections stained for succinic dehydrogenase, which permits the periportal, acinar zone 1 to be distinguished from the pericentral zone 3, counts were made of the zonal distribution of fluorescent, intact cancer cells and, by default, the numbers of "lost" cells. Very few intact cancer cells leave the liver from the single bolus of the intrasplenic injection, and even fewer of these generate pulmonary lesions; therefore, within the time limits of these experiments, the liver is virtually a closed system. A dynamic view of intrahepatic cancer-cell traffic with respect to zones 1 (periportal) and 3 (pericentral) was obtained from static measurements of cell densities at different times after intrasplenic injection, by means of Markov chain probability analysis. This indicated that, during the first hour after arrival in zone 1 of the liver sinusoids, there is a 10% probability of a B16F10 cell remaining intact in zone 1, an 89% probability of cell death in zone 1 and only a 1% probability of the cell passing into zone 3. During the same period, there is a 77% probability of an M5076 cell remaining intact in zone 1, a 21% probability of death, and a 2% probability of relocation to zone 3. In both cell types, very few cells were lost from zone 3. Further proportional death in zone 1 diminished over the next 23 hr, concomitant with an increased proportion of cell death in zone 3. Our results indicate that, although there is considerable variation between the 2 cell types studied here, most (B16) or many (M5076) of these cancer cells entering the liver via the portal vein die within 1 hr in zone 1 of liver lobules. In addition, very few of the cells delivered to zone 1 travel along the sinusoids to zone 3, and few of these reach the lungs in a viable state.