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.
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
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D000230:Adenocarcinoma; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D018093:Gelatinases / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008970:Molecular Weight; D009479:Neuropeptides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D009479:Neuropeptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9