MT1-MMP and MMP-2 mRNA expression in human ovarian tumors: Possible implications for the role of desmoplastic fibroblasts

Saliha Afzal, El Nasir Lalani, Richard Poulsom, Andrew Stubbs, Gail Rowlinson, Hiroshi Sato, Motoharu Seiki, Gordon W.H. Stamp

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85 Citations (Scopus)


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-labaled riboprobes was used to analyze 33 human ovarian tumors and mouse xenografts of human ovarian (DOVB 13, SKOV 3) and breast (MCF7) 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 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 fibroplasts may be the primary mediators of extracellular matrix remodeling with respect to this system.

Original languageEnglish
Pages (from-to)155-165
Number of pages11
JournalHuman Pathology
Issue number2
Publication statusPublished - 1998


  • Desmoplasia
  • Fibroblast
  • Invasion
  • MMP- 2
  • MT1-MMP
  • Matrix metalloproteinase
  • Ovarian
  • Remodeling
  • Stroma
  • Xenograft


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