A comparison of the expression of the malignant phenotype in two androgen-independent human prostate cancer cell lines after orthotopic implantation in nude mice

Abstract

Expression of some features of the malignant phenotype were compared in the DU145 and PC-3M human prostate cancer cell lines after their intraprostatic growth in nude mice. At necropsy, 27/74 (36%) mice injected with DU145 cells and 41/75 (55%) injected with PC-3M cells had either invasive macroscopic tumors, or microscopic intraprostatic tumor cell nests (p = 0.02). Para-aortic lymph node metastases had occurred in 19% of the DU145 cell, and 44% of the PC-3M cell tumor-bearing animals (p = 0.033). Immunohistochemical staining showed high mutant p53 and vascular endothelial growth factor (VEGF) expression by DU145 cells; PC-3M cells did not express detectable p53, and had relatively low VEGF immunohistochemical reactivity. Assays by ELISA established a statistically significant difference in VEGF levels between the cell lines (p < 0.001). Urokinase-like plasminogen activator (uPA) levels, determined by ELISA, were ten-fold higher in the PC-3M cell tumors, as were matrix metalloproteinase-9 (MMP-9) activities assessed by zymography. These findings of high expression of uPA and MMP-9, two key proteolytic enzymes in the invasive/metastatic process, by PC-3M cell prostatic tumors are consistent with their aggressive behavior; the low VEGF levels compared with those in the poorly metastatic DU145 cell tumors suggest that other angiogenic factors may be critical for prostate cancer cell progression in this model.