| Popis: |
Prostate cancer displays a high degree of variability in its rate of spread which may be due to differences in the invasive potential of the tumor cells. The degradation of the basal lamina (BL) and extracellular matrix is mediated in part by the secretion of matrix metalloproteinases (MMPs). Matrilysin (PUMP-1) has been shown to be over-expressed in prostate carcinoma. I have expressed matrilysin in the human prostate tumor cell line DU-145 to determine if matrilysin has a functional role in prostate tumor cell invasion. Transfected cell lines were assayed by an in vivo diaphragm model of tumor cell invasion. Vector-only transfected DU-145 cells injected i.p. into SCID mice invaded 11% of the the diaphragms whereas matrilysin transfected DU-145 cells invaded 66% of the diaphragms. The difference between the controls and matrilysin transfected cells was statistically significant (p < 0.006). These results suggest a functional role for matrilysin in the initial invasion of prostate cancer through the BL. Matrilysin may act by activating other proteinases in a cascade or by degrading the ECM and the ECM fragments inducing expression of other proteinases. The expression of matrilysin in the involuting rat uterus led to the hypothesis that matrilysin may be expressed in the prostate following castration. We assayed RNA from rat ventral prostates (RVP) of normal and castrated rats by northern analysis during an eight day time course for expression of the matrilysin, tissue inhibitor of metalloproteinase-1 (TIMP-1) and urokinase messages. Matrilysin was undetectable in normal RVP, however, five days after castration there was a significant increase in the matrilysin mRNA. The mRNA for TIMP-1 also peaked at five days after castration. The urokinase-type plasminogen activator mRNA was also elevated following castration with a peak five days post-castration. There was a low basal level of matrilysin protein present in the RVP which increased and peaked three days after castration. This combination of genes expressed in the RVP may play a role in the tissue remodeling following castration as well as in normal prostate epithelial cell turnover. |
