C-CAM1 expression: Differential effects on morphology, differentiation state and suppression of human PC-3 prostate carcinoma cells

Studies in rat prostate and liver have suggested that C-CAM1 is involved in the formation and maintenance of histotypic associations in tissues and po ssibly tumors. Most recently, C-CAM1 has been shown to suppress tumorigenic ity of prostate and colon carcinoma cells. However, the mechanisms whereby C-CAM1 suppresses growth and the relationship of this activity to its propo sed role in histotypic interactions remain largely unknown, In the present study, we have analysed the growth, phenotypic, morphological and ultrastru ctural characteristics of four human PC-3 prostate carcinoma cell lines tra nsduced with C-CAM1 retrovirus. We report that three of four lines regained their tumorigenic phenotype in vivo while maintaining high levels of C-CAM 1 expression and a growth retarded phenotype ill vitro. These findings sugg ested that high levels of C-CAM1 expression were negatively influencing rec overy during reconstitution after freezing or during the latency period aft er subcutaneous injection and that loss of suppression resulted from change s in expression of other molecules required for full disclosure of C-CAM1 m ediated growth inhibition, Results from Northern blot and immunofluorescenc e analyses of tumor nodules demonstrated that C-CAM1 decreased rather than enhanced phenotypic differentiation and induced ultrastructural and morphol ogical changes that occurred independently of tumor suppression.