Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase

Int J Cancer. 2005 Mar 10;114(1):19-31. doi: 10.1002/ijc.20697.


Although matrilysin (MMP-7) is overexpressed in various malignancies, few studies have evaluated its role in epithelial ovarian cancer (EOC) invasion and metastasis. We report that the secretion of MMP-7 in EOC is stimulated significantly by vascular endothelial growth factor (VEGF) and interlukin-8 (IL-8). We also examined the in vivo expression of MMP-7 in EOC and its effects on the in vitro invasion and progelatinase activation. We report that MMP-7 is overexpressed in ovarian cancer cell lines and EOC surgical specimens. DOV13 cells incubated with active rhMMP-7 significantly increased cellular invasion and proMMP-2 activation. RhMMP-7 also showed the ability to activate proMMP-2 and proMMP-9 in immortalized ovarian epithelial cell (IOSE-29) conditioned medium. In addition, rhMMP-7 was able to activate progelatinase in a concentration-dependent manner in vitro. TIMP-2 or the generic MMP inhibitor-GM6001 inhibited both the activation of proMMP-2 and the increased invasion of DOV13 cells promoted by rhMMP-7. By incubation of MMP2-TIMP-2 complex with equal molar rhMMP-7, MMP-2 was dissociated from the complex and activated in a time-dependent manner, suggesting that TIMP-2 helps to keep the latency of MMP-2. TIMP-2 also showed inhibitory effects on the MMP-7 induced increase of gelatinolytic activity in DOV13 and IOSE-29 conditioned media. A strong co-localization of MMP-7 and MMP-2 was observed in DOV13 cells and ovarian carcinoma permanent tissue sections. These results indicate MMP-7 is overexpressed in malignant ovarian epithelium and suggest MMP-7 may facilitate tumor cell invasion in vivo partly through the induction of progelatinase activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Carcinoma / enzymology*
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Collagenases / metabolism
  • Dipeptides / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Precursors / drug effects
  • Enzyme Precursors / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Gelatinases / drug effects
  • Gelatinases / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 7 / metabolism*
  • Matrix Metalloproteinase 7 / pharmacology
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / drug effects
  • Metalloendopeptidases / metabolism*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology*
  • Protease Inhibitors / pharmacology
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism


  • Antineoplastic Agents
  • Dipeptides
  • Enzyme Precursors
  • Interleukin-8
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Protease Inhibitors
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • pro-matrix metalloproteinase 9
  • progelatinase
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 9