Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system

Cancer Res. 1996 Nov 15;56(22):5279-84.


Matrix metalloproteinases (MMPs) have been implicated in tumor progression, but the exact roles that each member of this family may play in contributing to the behavior of malignant tumors are only beginning to be understood. MMP-9 (gelatinase B or the 92-kDa gelatinase/type IV collagenase) expression has been associated with metastasis in a variety of model systems including that of rat sarcomas generated by transformation of rat embryo cells with rasH and myc. To determine the effect that expression of MMP-9 has in this system, we inhibited the expression of MMP-9 using a hammerhead ribozyme. Introduction of an expression vector for a ribozyme directed against the rat MMP-9 mRNA sequence into a metastatic rat embryo cell line transformed by rasH and myc (2.10.10) that constitutively secretes MMP-9 resulted in the absence of detectable MMP-9 mRNA and loss of released 92-kDa gelatinase activity. These cells were no longer metastatic in a lung colonization assay but retained tumorigenicity. Introduction of an expression vector for a control hammerhead ribozyme had no effect. These data document the requirement for MMP-9 expression in metastasis in this system.

Publication types

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

MeSH terms

  • Animals
  • Collagenases / metabolism
  • Down-Regulation
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • RNA, Catalytic / chemistry
  • RNA, Catalytic / genetics
  • RNA, Catalytic / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Sarcoma, Experimental / enzymology
  • Sarcoma, Experimental / secondary*
  • Transfection
  • Tumor Cells, Cultured


  • Matrix Metalloproteinase Inhibitors
  • RNA, Catalytic
  • RNA, Messenger
  • Collagenases
  • Matrix Metalloproteinase 9