Differential experimental micrometastasis to lung, liver, and bone with lacZ-tagged CWR22R prostate carcinoma cells.
LacZ-tagged human prostate carcinoma CWR22Rv1 cells metastasize spontaneously to lung, liver, and bone from subcutaneous primary tumors in athymic nude mice; these organs are 'natural' targets of metastasis for the human disease. To evaluate the mechanism(s) of metastasis to these organs, an experimental metastasis model was used by taking advantage of the ultrasensitive detection of lacZ. Within I h after tail vein injection, micrometastases were forming in lung, liver, bone, kidney, and brain with very different quantitative levels. The kinetics of loss of unstable micrometastases and retention of stable ones were also very different in these organs. After injecting suspensions of single cells, both whole-organ and serial-section staining for lacZ revealed considerable heterogeneity in cell number of individual lung micrometastases while micrometastases in liver contained only I or 2 cells. The size of individual bone micrometastases also suggested only 1 or 2 cells. Tumor cells could also be detected in the small blood vessels of the lung within minutes after injection. These studies indicate that lacZ-tagged CWR22Rv1 cells after tissue culturing contain subsets of cells capable of establishing transient micrometastases in lung, liver, and bone after direct injection into the animal's circulation. Moreover, the quantitative and qualitative properties of the micrometastases in the three organs differ significantly, suggesting different mechanisms for stabilization and fates of micrometastases in these organs.
Holleran
Julianne L
JL
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
Miller
Carson J
CJ
Edgehouse
Nancy L
NL
Pretlow
Theresa P
TP
Culp
Lloyd A
LA
D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D002999:Clone Cells / Q000637:transplantation; D017930:Genes, Reporter; D006801:Humans; D007275:Injections, Intravenous; D007763:Lac Operon; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000473:pathology*; D013623:Tail; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation