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 generate models of metastasis and formulate therapies.


METHODS
Prostate carcinoma cells PC-3.luc expressing the luciferase gene were intramuscularly inoculated in nude mice to generate experimental tumors. Metastatic cells in target organs were easily counted by their capacity to produce light.


RESULTS
Tumor cells were very mobile and migrated to all the target organs examined: lymph nodes, brain, bone, lungs, liver, kidney, spleen, testicles, prostate, seminal vesicle, and scrotum. Organ colonization started very early, 14 days after inoculation, when primary tumors were very small and produced 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 quantitatively described by power functions of time or primary tumor light-producing capacity. The ratio of metastatic TCEs to primary tumor TCEs clustered 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 started early before the third week postinoculation and when primary tumors had 2 x 10(4) TCEs. Tumor cells were found widely spread in all the organs tested. The possibility of easily quantifying tumor cell burden should make this approach useful for the study of metastasis and the development of antimetastatic therapies.
Rubio
N
N
Department of Cell Biology, Institut de Recerca Oncològica, Barcelona, Spain.
Villacampa
M M
MM
El Hilali
N
N
Blanco
J
J
D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000556:secondary; D001932:Brain Neoplasms / Q000556:secondary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000556:secondary; D008113:Liver Neoplasms / Q000556:secondary; D008156:Luciferases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology*; D012680:Sensitivity and Specificity; D013047:Specific Pathogen-Free Organisms; D013160:Splenic Neoplasms / Q000556:secondary; D013997:Time Factors; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D008156:Luciferases