Pattern and Load of Spontaneous Liver Metastasis Dependent on Host Immune Status Studied With a lacZ Transduced Lymphoma

Abstract

Detection of disseminated leukemia within organ is often very difficult and might lead to underestimation of the metastatic load. Therefore, we transduced the mouse ESb T lymphoma with the bacterial lacZ gene, which allowed us to follow metastasis at the single cell level. Intradermal primary tumor growth of lacZ transduced ESbL cells (L-CI.5s) comprised three phases: an initial expansion phase (day 0 to 9, increase from 0 to 8 mm, tumor diameter), a plateau phase (day 9 to 20, constant diameter of 8 mm and necrosis), and a second expansion phase (day 20 to 30, increase from 8 to 15 mm). Liver metastasis could already be detected at day 3 and maintained at that level until day 23, where exponential expansion started. A distinct mosaic-like metastasis pattern developed, with preferential localization of tumor cells to the periportal areas of the liver in immunocompetent animals. In contrast, in immunocompromised mice, primary tumor growth and metastasis were progressive and metastasis appeared as diffuse or focal/clustered. Healthy animals surviving a tumor cell inoculum of a variant cell ESbL-CI.5) with a reduced metastatic potential carried low levels of possibly dormant tumor cells in the bone marrow. Thus, this study showed that host immunocompetence determines to a large extent kinetics and load of spontaneous liver metastases and even influences the pattern and localization of disseminated lymphoma cells.