Heterogeneous Subpopulations of Human Prostatic Adenocarcinoma Cells: Potential Usefulness of P21 Protein as a Predictor for Bone Metastasis

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Abstract
Expression of the p21 protein of the ras oncogene family was studied in a case of human prostatic adenocarcinoma tissue and the cell line was derived from the primary tumor. Flow cytometry analysis of the tumor cells obtained from the primary tumor indicated that approximately 25 percent of the cells were positive for this oncogene product. However, by the immunoperoxidase method almost all of the tumor cells at the vertebral metastatic sites in the same patient were positive for the p21 protein. The cell line established from the primary tumor displayed 2 distinct subpopulation growth patterns in vitro: a monolayer, density-inhibited growth and a multicellular aggregate type growth morphology. These 2 subpopulations could be separated by density elutriation centrifugation. The isolates subpopulation cells were noted to express prostatic acid phosphatase and prostate specific antigen at high frequency. High levels of expression of these 2 prostatic markers also were found in the tumor cells at the vertebral metastatic sites. However, when the isolated subpopulations were analyzed for the expression of p21 protein, the multicellular grown cells were almost 90 percent positive for the p21 antigen, whereas only approximately 5 percent of the monolayer grown cells were positive for the same protein. Our findings suggest that primary prostatic carcinomas are composed of heterogeneous subpopulations of neoplastic cells while only specific subpopulations have metastatic potential. Quantification of prostatic acid phosphatase and prostate specific antigen in the primary tumor cells probably will not offer a predictive value for the eventual behavior of the tumors. However, evaluation of oncogene products, such as the p21 protein, may be useful as a clinical predictor for metastatic potential.