PATTERN AND LOAD OF SPONTANEOUS LIVER METASTASIS DEPENDENT ON HOST IMMUNE STATUS STUDIED WITH A LACZ TRANSDUCED LYMPHOMA

Detection of disseminated leukemia within organs is often very difficu lt 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. Intra dermal primary tumor growth of lacZ transduced ESbL cells (L-Cl.5s) co mprised 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, consta nt diameter of 8 mm and necrosis), and a second expansion phase (day 2 0 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 exp onential expansion started. A distinct mosaic-like metastasis pattern developed, with preferential localization of tumor cells to the peripo rtal areas of the liver in immunocompetent animals. In contrast, in im munocompromized mice, primary tumor growth and metastasis were progres sive and metastasis appeared as diffuse or focal/clustered. Healthy an imals surviving a tumor cell inoculum of a variant cell (ESbL-Cl.5) wi th a reduced metastatic potential carried low levels of possibly dorma nt tumor cells in the bone marrow. Thus, this study showed that host i mmunocompetence determines to a large extent kinetics and load of spon taneous liver metastases and even influences the pattern and localizat ion of disseminated lymphoma cells. (C) 1994 by The American Society o f Hematology.