Tumor progression, micrometastasis, and genetic instability tracked with histochemical marker genes.
Mouse fibrosarcoma (3T3 cells transfected with different oncogenes), human neuroblastoma, or human prostate carcinoma cells have been genetically-tagged with different histochemical marker genes (E. coli lacZ, placental alkaline phosphatase, or Drosophila alcohol dehydrogenase). Injection into athymic nude mice permits their tracking at all stages of primary tumor formation and micrometastasis to various organs at the single-cell level. Two different tumor classes, tagged with different marker genes, can be tracked together. Primary tumors display regional dominance of one tumor class with exclusion of other classes. During micrometastasis, tumor cells are detected binding to the endothelium of lung blood vessels, followed by establishment of multiple-cell micrometastases. Micrometastases in some organs are transient while in other organs there is differential expansion into overt metastases. Tagged tumors also reveal the timing of angiogenesis of developing primary tumors and overt metastases. In all three tumor systems, there are three classes of genetic stability of marker gene expression in clonal populations-high stability, intermediate stability, and high instability. Instability in marker gene expression in one tagged prostate carcinoma system does not depend on a hypermethylation mechanism, suggesting a genetic basis for loss of activity. Use of histochemical marker genes, combined with laser-capture microdissection and various PCR methods, can now be used to evaluate gene activities in single or multiple tumor cells in virtually any organ and primary tumor of the animal model system.
D000818:Animals; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology