Abstract
Abstract : Metastasis is the leading cause of the death in cancer patients. Cell motility is believed to be a necessary step in the metastatic process. Currently, most methods available to study the behavior of metastatic tumor cells are indirect, e.g., cell motility is examined in vitro and the results are correlated with metastatic capability. We have developed a model that directly examines the motility of metastatic primary tumor cells in situ. A metastatic rat breast cancer cell line was established that constitutively expresses the green fluorescent protein (GFP). Upon subcutaneous injection of these cells into the mammary fat pad of female Fischer 344 rats, primary tumors and subsequent metastases form that fluoresce when excited with light passed through an FITC filter set. Animations of metastatic tumor cells moving in live rats were generated by intravital imaging of the primary tumor, in situ, on a laser scanning confocal microscope. With this model, the behavioral phenotype of tumor cells can be described and the effects of genetic manipulations or therapeutic treatments on this phenotype can be determined. This is the first report of visualization of cells in a primary tumor in live animals in a clinically relevant model.
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