Metastatic burden in nude mice organs measured using prostate tumor PC-3 cells expressing the luciferase gene as a quantifiable tumor cell marker

BACKGROUND. Sensitive procedures for quantitative measurement of tumor cell spread as a function of time and primary tumor size are necessary to gener ate models of metastasis and formulate therapies. METHODS. Prostate carcinoma cells PC-3.luc expressing the luciferase gene w ere intramuscularly inoculated in nude mice to generate experimental tumors . Metastatic cells in target organs were easily counted by their capacity t o produce light. RESULTS. Tumor cells were very mobile and migrated to all the target organs examined: lymph nodes, brain, bone, lungs, liver, kidney, spleen, testicle s, prostate, seminal vesicle, and scrotum. Organ colonization started very early, 14 days after inoculation, when primary tumors were very small and p roduced an amount of light equivalent to that generated by 2 x 10(4) tumor cells in vitro (tumor cell equivalents, TCEs). Tumor cell burden could be q uantitatively described by power functions of time or primary tumor light-p roducing capacity. The ratio of metastatic TCEs to primary tumor TCEs clust ered around organ characteristic values: 10(-3) for femur and lumbar lymph nodes, 10(-6) for the spleen, and 10-3 for the added set of organs. CONCLUSIONS. Dispersal of PC-3 tumor cells from IM experimental tumors star ted early before the third week postinoculation and when primary tumors had 2 x 104 TCEs. Tumor cells were found widely spread in all the organs teste d. The possibility of easily quantifying tumor cell burden should make this approach useful for the study of metastasis and the development of antimet astatic therapies. Prostate 44:133-143, 2000. (C) 2000 Wiley-Liss, Inc.