Document Detail

MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: possible implications for the role of desmoplastic fibroblasts.
MedLine Citation:
PMID:  9490275     Owner:  NLM     Status:  MEDLINE    
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.
S Afzal; E N Lalani; R Poulsom; A Stubbs; G Rowlinson; H Sato; M Seiki; G W Stamp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human pathology     Volume:  29     ISSN:  0046-8177     ISO Abbreviation:  Hum. Pathol.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-03-05     Completed Date:  1998-03-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421547     Medline TA:  Hum Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  155-65     Citation Subset:  IM    
Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
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MeSH Terms
Actins / analysis,  metabolism
Adenocarcinoma / enzymology*,  pathology
Adenofibroma / enzymology,  pathology
Fibroblasts / enzymology,  pathology
Gelatinases / genetics,  metabolism*
In Situ Hybridization
Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / genetics,  metabolism*
Mice, Nude
Ovarian Neoplasms / enzymology*,  pathology
RNA, Messenger / metabolism*
Transplantation, Heterologous / pathology
Tumor Cells, Cultured
Tumor Markers, Biological / metabolism
Reg. No./Substance:
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 Metalloproteinase 2; EC Metalloproteinase 14

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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