At autopsy approximately 10-30% of all males over 50 years of age have pathological evidence of prostate cancer which indicates that 11,000,000 U.S. males presently harbor latent forms of prostate cancer. Fortunately, only a small percent will develop the clinically manifest form and this yields 96,000 new cases per year, making this the second leading cause of cancer deaths. Fine needle aspiration makes it easier to obtain prostate cancer cells in an out-patient setting and at present we are urgently in need of a method to distinguish the clinically aggressive forms of prostate cancer from the nonaggressive latent forms. This application focuses on the application of a new method to quantitate and analyze various types of tumor cell motility which appear to be promising in determining the metastatic potential of prostate cancer cells. We will utilize the spontaneous animal model of prostate cancer (Dunning R3327) having a wide variety of metastatic properties that have been well characterized in our laboratory. It has been possible to assess the quantitative nature of the cell motility in this model and to relate it to metastatic potential of these cells. The quantitative assessment of the cell motility includes various types of vectorial motion, pseudopodal extension, membrane undulation and ruffling. This analytical approach involves capturing time-lapse videomicroscopy images and analyzing them by a 2-dimensional Fourier transformation in which both the spatial and temporal harmonics will be assessed in a quantitative manner. This imaging system will be applied to fresh aspirated cell from both primary and metastatic lesions in the Dunning tumor model. Nonmotile and nonmetastatic Dunning tumor cells will be compared to highly motile and metastatic variants in relation to their shape, motility pattern, intracellular calcium level and cell surface charge. We have been able to transfect the nonmotile and nonmetastatic variants with a viral-Harvey-ras oncogene which converts them to a high metastatic phenotype. In a comparative study, we will use this system to analyze changes in the cell motility pattern of HL-60, MCF-7 breast cancer cells, NIH-3T3 cells and NRK cells before and after transfection with the viral-H-ras oncogene. For 100 years pathologist have diagnosed and identified cancer by microscopic analysis of fixed, dead tissues. Our analysis is being extended to live cells to reflect the biological properties of the tumor. This approach has application to basic tumor biology as well as to developing a new system that is applicable to aspiration biopsies that can be applied to human prostate cancer.
