Neuropeptides induce Mr 92,000 type IV collagenase (matrix metalloprotease-9) activity in human prostate cancer cell lines.

The type IV collagenases matrix metalloprotease (MMP)-2 and MMP-9 are linked with a wide array of biological activities, including tumor invasion, metastasis, and angiogenesis. Here, we report that neuropeptide hormones, which are present in prostatic adenocarcinomas, can stimulate secreted activity of MMP-9 in human prostate cancer cell lines. Northern blotting analyses demonstrated that neuropeptide stimulation lead to elevated mRNA levels of MMP-9 but not MMP-2. Further assays of MMP-9 promoter activation and a nuclear run-off indicated that neuropeptide induction of MMP-9 expression occurs at the level of transcription. These data indicate that neuropeptides can regulate MMP activity, which, in turn, could facilitate prostate cancer progression.