NEUROPEPTIDES INDUCE M-R-92,000 TYPE-IV COLLAGENASE (MATRIX METALLOPROTEASE-9) ACTIVITY IN HUMAN PROSTATE-CANCER CELL-LINES

The type HV collagenases matrix metalloprotease (MMP)-2 and MMP-9 are linked with a wide array of biological activities, including tumor inv asion, metastasis, and angiogenesis. Here, vie report that neuropeptid e hormones, which are present in prostatic adenocarcinomas, fan stimul ate secreted activity of MMP-9 in human prostate cancer cell lines. No rthern blotting analyses demonstrated that neuropeptide stimulation le ad to elevated mRNA levels of MMP-9 hut not MMP-2. Further assays of M MP-9 promoter activation and a nuclear run-off indicated that neuropep tide induction of MMP-9 expression occurs at the level of transcriptio n, These data indicate that neuropeptides can regulate MMP activity, w hich, in turn, could facilitate prostate cancer progression.