The objective of this study is to elucidate the relationship between expression of pathobiologically relevant surface components of human prostatic carcinoma cells and tumor cell behavior. The appropriate monoclonal antibodies will be used to detect the expression of specific cell surface components and as selective agents to enrich for cells with or without a given surface component. A panel of human prostate carcinoma cell clones derived from established lines, which are positive or negative with respect to surface expression of each determinant detected by the monoclonal antibodies, will be established. Cell clones that vary quantitatively in expression of each cell surface component under study will be compared in terms of tumorigenicity, growth rate, and metastatic behavior in athymic nude mice. These data will be supplemented by identification of factors that regulate expression of any prostate tumor-related cell surface component affecting in vivo or in vitro characteristics of the parental line. A highly reproducible model of spontaneous lymphatic and pulmonary metastasis by human prostate carcinoma cells growing in nude mice has been established. The kinetics of metastasis, histopathology, and dose-response characteristics of this PC-3 subline have been determined, thus providing a reference system. Thus far, at least one less efficiently metastatic PC-3 subpopulation has been identified and characterized in vivo and in vitro. Treatment of PC-3 sublines with mutagens generated additional metastatic phenotypes. Thus, both naturally-arising and mutagen-induced phenotypes are now available for analysis of cell surface components. Identification of the correlation(s) between the presence or absence of prostate tumor, cell-related, cell-surface components and biological behavior of the cells in the nude mouse will permit identification of specific molecular entities involved in prostate tumor growth and metastasis. (A)
