CELL MOTILITY OF TUMOR-CELLS VISUALIZED IN LIVING INTACT PRIMARY TUMORS USING GREEN FLUORESCENT PROTEIN

Metastasis is the leading cause of death in cancer patients. Cell moti lity is believed to be a necessary step in the metastatic process (L. Liotta and W. G. Stetler-Stevenson, In: Cancer: Principles and Practic e of Oncology, pp. 134-149, 1993). Currently, most methods available t o study the behavior of metastatic tumor cells are indirect, e.g., cel l motility is examined in vitro and the results are correlated with me tastatic capability (A. W. Partin, et at, Cancer Treat. Res., 59: 121- 130, 1992). We have developed a model that directly examines the motil ity of metastatic primary tumor cells in situ. A metastatic rat breast cancer cell line was established that constitutively expresses green fluorescent protein. Upon s.c. injection of these cells into the mamma ry fat pad of female Fischer 344 rats, primary and metastatic tumors f orm that fluoresce when they are excited with FITC-filtered light. Ani mations of metastatic tumor cells moving in live rats mere generated b y intravital imaging of the primary tumor bt situ on a laser scanning confocal microscope. With this model, the behavioral phenotype of meta static and nonmetastatic tumor cells can be described and determined. This information will allow the effects of genetic manipulations or th erapeutic treatments on this phenotype to be determined (D. R. Soll, I nt. Rev. Cytol., 163: 43-104, 1995). This is the first time that livin g primary tumor cells in a live animal have been visualized as part of a clinically relevant model.