Cancer cell traffic from the lungs to the liver: An example of metastatic inefficiency

It is probable that metastasis is an inefficient process in terms of cancer cells. One cause of this inefficiency may be that cancer cells temporarily arrested in one organ are «processed» by it, so that they die before or shortly after arrival in another organ. In the present experiments, the lung‐to‐liver traffic of [ 125 I]dUrd‐labelled W‐256 cancer cells is examined over the course of 27 h in tumor‐bearing and non‐tumor‐bearing rats, following injection into, and sampling from, various points in the cardiovascular system. Following tail‐vein injections, W‐256 are temporarily arrested in the lungs and slowly released; some of the released cells are then temporarily arrested in the liver. Two percent of the cells detected in the lungs are non‐viable compared with approximately half of those in the liver; these measurements of viability correlate with a higher (10:I) incidence of lung transplants over liver transplants, and with the observation that extrapulmonary metastases are uncommon with this tumor. Direct injections of cancer cells into the liver indicate that the reduced viability of cancer cells at this site is not due to an inherently hostile hepatic environment. Injections into and sampling from, other sites indicate that only small proportions of cells were killed on their way to the lungs, during their arrest in the pulmonary capillaries and arterioles, or between the left ventricle, aorta, hepatic artery and liver. Pretreatment of W‐256 cells with neuraminidase, which is expected to make them more deformable, did not affect the viability of cells in the liver, thereby arguing against «processing» occurring during transit in the pulmonary circulation distal to the initial arrest sites. By a process of elimination it is concluded that a significant amount of trauma resulting in cancer cell death occurs during the events culminating in their release from temporary arrest sites at the pulmonary vascular endothelium. As the lungs are commonly the first organ encountered by circulating tumor cells, it is suggested that the low viability of cells released from the lungs contributes to metatastic inefficiency.