CORRELATION OF METASTASIS-RELATED GENE-EXPRESSION WITH METASTATIC POTENTIAL IN HUMAN PROSTATE CARCINOMA-CELLS IMPLANTED IN NUDE-MICE USING AN IN-SITU MESSENGER-RNA HYBRIDIZATION TECHNIQUE

The purpose of this study was to determine whether the expression leve l of several metastasis-regulating genes correlates with the metastati c potential of human prostate cancer cells implanted into the prostate of nude mice. The steady-state mRNA expression levels for epidermal g rowth factor receptor (EGFR; growth), basic fibroblast growth factor ( bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV c ollagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimet ric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials. Highly metastatic cells growing in culture constitutively and uniformly expressed highe r levels of bFGF, IL-8, type IV collagenase, and mdr-1 mRNA transcript s than parental PC-3M cells or low metastatic cells, which displayed a heterogeneous pattern of gene expression. Human prostate cancer cells implanted in nude mice at an ectopic site (subcutaneous) expressed lo wer levels of EGFR, mdr-1, bFGF, IL-8, and collagenase type IV than th ose implanted in an orthotopic site (prostate), indicating that the ex pression of these genes was dependent on the organ environment. Highly metastatic cells growing in the prostate expressed higher levels of E GFR, bFGF, type IV collagenase, and mdr-1 mRNA than low metastatic par ental cells in the same site. These data demonstrate a direct correlat ion between the expression of several metastasis-related genes and the metastatic potential of human prostate cancer cells in nude mice and suggest that multiparametric in situ hybridization analyses can be use d to identify the metastatic potential of individual patients' prostat e cancers.