Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive

In metastasis research, modern microscopic techniques shed a new light on the mechanisms of metastatic tumor cell arrest in the microcirculation of potential metastasis target organs. In this study, we differentiated the contribution of mechanical cell arrest, determined as lumen occlusion of liver sinusoids by tumor cells, and specific cell adhesion mediated by integrins for the arrest of human colon cancer cells in rat livers.

Using in vivo microscopy, the diameters of liver sinusoids of two different rat strains (CD, 250-300 g and RNU, 80-120 g) were determined. Cells (HT-29LMM) were intracardially injected, and the numbers of arrested cells and the rates of sinusoid occluding cells were determined.

Mean sinusoid diameter in CD rats was 6.98 +/- 1.42 microm compared to 5.14 +/- 1.11 microm in RNU rats (p < 0.001). The numbers of arrested tumor cells and the rates of extravasated tumor cells did not differ between the two rat strains. Nevertheless, 5 and 30 min after cell injection, 35 +/- 15% and 19 +/- 8% of arrested cells, respectively, appeared lumen occluding in RNU rats and 9 +/- 6% and 3 +/- 3%, respectively, in CD rats (p < 0.05). Despite the higher rates of lumen occlusive cells in RNU rats, inhibition of beta-1 or beta-4 integrins significantly impaired cell arrest by 30-60% in both strains.

In summary, these results demonstrate that lumen occlusion alone, as determined by in vivo microscopy, is insufficient to establish stable tumor cell arrest of colon carcinoma cells in metastatic target organs and does therefore not rule out the requirement of specific adhesive interactions for tumor cell arrest in the microcirculation.