Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma

Am J Pathol. 1998 Feb;152(2):591-6.


Although a number of effective therapies are available for localized prostate cancer, metastatic prostate cancer is difficult to treat and impossible to cure. Identification of the gene products that enable a prostatic carcinoma cell to metastasize should facilitate an understanding of the processes leading to metastasis. To characterize the contribution of matrix metalloproteinase-9 (MMP-9, gelatinase B or the 92-kd type IV gelatinase/collagenase) to the development of metastasis in prostate cancer, we reduced MMP-9 expression in metastatic murine prostatic carcinoma cells using a ribozyme. The ribozyme transfected cells had lower basal levels of MMP-9 as well as decreased levels after stimulation by transforming growth factor-beta or phorbol 12-myristate 13-acetate when compared with the parental cells or with control transfectants. The cells with down-regulated MMP-9 were unable to form lung colonies in the experimental metastasis assay, whereas the controls and parental cells readily formed metastases. All cell types readily formed tumors after injection and down-regulation of MMP-9 did not adversely affect the rate of tumor growth. Thus, MMP-9 expression is required for hematogenous metastasis in a murine prostate model system raising the possibility that it may play an equivalent role in human prostate cancer.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma / metabolism*
  • Carcinoma / secondary*
  • Collagenases / genetics
  • Collagenases / metabolism*
  • Female
  • Gelatinases / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • RNA, Catalytic / genetics
  • RNA, Catalytic / physiology
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Transforming Growth Factor beta / pharmacology


  • RNA, Catalytic
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Collagenases
  • Gelatinases
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate