Tracking micrometastasis to multiple organs with lacZ-tagged CWR22R prostate carcinoma cells.
Metastasis to organs other than lung is rarely observed in animal model systems of human prostate carcinoma (PCA), with the exception of already metastatic isolates of human PCA cultured for long periods of time. To analyze more directly the evolution of metastatic variants from primary PCA tumor isolates, the lacZ histochemical marker gene was transfected into the CWR22Rv1 cell line isolated from the CWR22R xenograft (primary tumor). Three clones of varying lacZ-expression stability were analyzed for tumorigenicity and progression in athymic nude mice. Clones B and D were highly tumorigenic in the subcutis; however, lacZ expression was highly unstable. In contrast, clone H demonstrated highly stable lacZ expression for >25 passages in culture or in animals. Clone H, injected sc in a PBS vehicle, gave a 15-40% tumorigenic take. All primary tumor-bearing animals exhibited micrometastases in lung and other organs. Clone H injected in a Matrigel vehicle gave 100% tumorigenicity, with all animals displaying micrometastases in lung, liver, and/or bone (lower frequency in brain and kidney). Overall, the relative frequency of micrometastasis to multiple organs was lung>liver=bone>>brain>kidney. Overt metastases were never observed in the lung or bone but were occasionally found in liver. lacZ-transfected clone H CWR22Rv1 cells represent a much more accurate model of metastasis of PCA to the organs normally involved in progression of the human disease. Use of marker gene-tagged cells and other high-resolution molecular techniques will now permit analyses of the earliest events in PCA progression and micrometastasis.
Holleran
J L
JL
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
Miller
C J
CJ
Culp
L A
LA
D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D002455:Cell Division; D002999:Clone Cells; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D007763:Lac Operon / Q000235:genetics*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D005819:Genetic Markers