| MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts. | |
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MedLine Citation:
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PMID: 9490275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Expression of activated MMP-2 (72 kDa type IV collagenase) is highly associated with the malignant phenotype in adenocarcinomas, but predominant expression of the mRNA appears to be in stromal cells. MT1-MMP (membrane type 1-matrix metalloproteinase) is implicated in tumor-epithelial cell surface activation of latent pro-MMP-2, indicating a mechanism for tumor-stromal interaction in invasion. We determined the relative mRNA distribution of these MMPs in human ovarian tumors with a view to analyzing potential variations in the epithelial-mesenchymal interactions dictating ovarian tumor cell spread. In situ hybridization using 35S-labeled riboprobes was used to analyze 33 human ovarian tumors and mouse xenografts of human ovarian (DOV 13, SKOV3) and breast (MCF 7) tumor cell lines known to express MT1-MMP and MMP-2. MMP-2 mRNA was expressed in 31 of 33 and MT1-MMP mRNA was expressed in 29 of 33 tumor cases. MMP-2 mRNA was predominantly expressed in desmoplastic fibroblasts and in the subepithelial stroma. MT1-MMP mRNA showed some colocalization with MMP-2 in stromal cells. Neoplastic epithelial cell labeling for MT1-MMP mRNA was present in borderline and malignant tumors but not in benign tumors, and was invariably less than stromal labeling. Xenografts of DOV 13, SKOV 3, and MCF 7 cells showed some stromal localization of MMP-2 mRNA and weak labeling of DOV 13 cells. There was variable labeling for MT1-MMP mRNA in the neoplastic cells only. The colocalization of MT1-MMP and MMP-2 mRNAs in ovarian carcinoma stroma supports the view that MT1-MMP is closely associated with MMP-2 expression and function. It suggests that either additional mechanisms are involved in regulating MMP-2 activation at the tumor cell surface, or more intriguingly, that desmoplastic fibroblasts may be the primary mediators of extracellular matrix remodeling with respect to this system. |
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Authors:
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S Afzal; E N Lalani; R Poulsom; A Stubbs; G Rowlinson; H Sato; M Seiki; G W Stamp |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human pathology Volume: 29 ISSN: 0046-8177 ISO Abbreviation: Hum. Pathol. Publication Date: 1998 Feb |
Date Detail:
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Created Date: 1998-03-05 Completed Date: 1998-03-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421547 Medline TA: Hum Pathol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 155-65 Citation Subset: IM |
Affiliation:
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Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
/
analysis,
metabolism Adenocarcinoma / enzymology*, pathology Adenofibroma / enzymology, pathology Animals Female Fibroblasts / enzymology, pathology Gelatinases / genetics, metabolism* Humans In Situ Hybridization Matrix Metalloproteinase 14 Matrix Metalloproteinase 2 Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases / genetics, metabolism* Mice Mice, Nude Ovarian Neoplasms / enzymology*, pathology RNA, Messenger / metabolism* Transplantation, Heterologous / pathology Tumor Cells, Cultured Tumor Markers, Biological / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Mmp14 protein, mouse; 0/RNA, Messenger; 0/Tumor Markers, Biological; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.80/Matrix Metalloproteinase 14 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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