TRAFFIC TO LYMPH-NODES OF PC-3 PROSTATE TUMOR-CELLS IN NUDE MISE VISUALIZED USING THE LUCIFERASE GENE AS A TUMOR-CELL MARKER

Tumor cell traffic between intramuscular tumors experimentally induced in nude mice and lymph nodes was studied using PC-3.luc prostate aden ocarcinoma cells permanently transfected with the luciferase gene as a tumor cell marker. This sensitive approach allowed the detection of 1 luminescent tumor cell mixed with 1.10(7) unlabeled PC-3 cells and of 1 tumor cell/lymph node. PC-3.luc cells inoculated in nude mice showe d a 1000-fold expansion, accompanied by a 4.5-fold increase in tumor c ell density (tumor cell number/gram of tumor), during the first 90 day s of primary tumor growth. No macroscopic secondary tumors were found in organs, other than lymph nodes, by the end of the experiment. Tumor cell spread to lymph nodes was detected at Day 21, when there were 2. 10(5) tumor cells at the inoculation sites, before discrete primary tu mors could be identified. The total tumor cell burden in the tested ly mph nodes was modeled by a power function of primary tumor cell number (determination coefficient R-2 = 0.9472). By the end of the experimen t, on Day 110, there were 1.8 metastatic cells in the studied lymph no des for every 1000 primary tumor cells. These results suggest that emp irically obtained tumor-specific indexes could be used to characterize the invasion of lymph nodes by tumor cells. The path of spread for PC -3.luc cells from intramuscular sites appears to follow the lymphatic system, and at no time during the experiment were tumor cells found in blood. An upper limit of no more than 16 blood-circulating tumor cell s was established for these experiments. The observation of tumor cell s that were invading the lymphatic system from the onset of tumor grow th but unable to establish secondary tumors in other organs emphasizes the potential of this procedure in studying the multi-step nature of metastasis.