Infiltration of tumour cells into cultures of isolated hepatocytes.

MB 6A lymphosarcoma and TA3 mammary carcinoma cells have previously been shown to infiltrate from liver blood vessels, where they had been arrested, into the liver parenchyma. The same tumour cells were previously added to cultures of isolated hepatocytes, 24 h after their isolation. Both tumour cell types adhered to both dorsal and lateral surfaces of hepatocytes. The lymphosarcoma cells rapidly infiltrated between the hepatocytes. They first extended pointed pseudopods between the liver cells, and when the tumour cell body intruded, they deeply invaginated the liver cells at an interhepatocyte boundary. The MB A6 cells accumulated between and under the hepatocytes, and after 24 h virtually all cells were contained within the cultures. TA3 cells also invaginated hepatocytes, not only at interhepatocyte boundaries, but all over the exposed surface. They did not extent pseudopods. The process was much slower than with MB 6A cells: After 24 h a few TA3 cells were completely encircled by hepatocytes. These observations indicate that the mechanism of infiltration is different from the 2 tumour cell types. Part of the TA3 cell did not invaginate the hepatocytes. Several of these cells spread on th hepatocyte surface, attaining a flattened shape. TA3 cells formed extensive tight junctions with the hepatocytes, sometimes sealing an intercellular lumen that resembled both a tumour acinus and a bile canaliculus. Also desmosomes were occasionally formed. The hepatocyte cultures appear to be a suitable model for studying the mechanism of liver infiltration, not only of tumour cells, but also leucocytes.