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.
Sehgal
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Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Thompson
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TC
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