Coincident implantation, growth and interaction sites within the liver of cancer and reactive hematopoietic cells

We have examined the anatomical‐functional sites within mouse liver where phenylhydrazine (PHZ)‐induced hematopoietic foci, and M5076 reticulum cell sarcoma, B 16F10 melanoma and Lewis lung‐carcinoma cells specifically develop as colonies after intrasplenic injection. Cancer foci occurred predominantly in the 2. 4 to 4. 0 segment of the sinusoidal pathway, corresponding to hepatic acinar zone I. No significant differences were detected between different types of tumor, including their different tendencies to spontaneously metastasize liver, or as a result of the different procedures used for obtaining foci or metastases. In addition, PHZ‐treatment of mice previously injected with tumor cells, resulted in double colonization of the liver tissue by both hematopoietic and cancer cells, predominantly in zone I. This spatial coincidence indicates that non‐cancer‐specific mechanisms operate in zone I, either promoting implantation and/or growth of cell colonies or, alternatively, inhibiting these processes in the region surrounding the central vein (Rappaport zone 3). Our observations failed to reveal mutual displacement of cancer or hematopoietic foci by potential competition for development sites in zone I. Enumeration and diameter measurements of cancer foci in PHZ‐treated animals showed that the presence of hepatic hematopoietic foci coincided with a significant increase in the hepatic metastasis volume. However, the fact that no significant differences in pulmonary metastases occurred in both the PHZ‐treated and control mice given tail‐vein injection of cancer cells, and that PHZ reduces cancer cell proliferation in vitro, reveal evidence of local interactions with hematopoietic foci which promote growth of cancer foci in liver.