Activation of pro-gelatinase B by endometase/matrilysin-2 promotes invasion of human prostate cancer cells

J Biol Chem. 2003 Apr 25;278(17):15056-64. doi: 10.1074/jbc.M210975200. Epub 2003 Feb 13.


This work has explored a putative biochemical mechanism by which endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) may promote human prostate cancer cell invasion. Here, we showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. The role of MMP-26 in prostate cancer progression is unknown. MMP-26 was capable of activating pro-MMP-9 by cleavage at the Ala(93)-Met(94) site of the prepro-enzyme. This activation proceeded in a time- and dose-dependent manner, facilitating the efficient cleavage of fibronectin by MMP-9. The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested. To investigate the contribution of MMP-26 to cancer cell invasion via the activation of MMP-9, highly invasive and metastatic human prostate carcinoma cells, androgen-repressed prostate cancer (ARCaP) cells were selected as a working model. ARCaP cells express both MMP-26 and MMP-9. Specific anti-MMP-26 and anti-MMP-9 functional blocking antibodies both reduced the invasiveness of ARCaP cells across fibronectin or type IV collagen. Furthermore, the introduction of MMP-26 antisense cDNA into ARCaP cells significantly reduced the MMP-26 protein level in these cells and strongly suppressed the invasiveness of ARCaP cells. Double immunofluorescence staining and confocal laser scanning microscopic images revealed that MMP-26 and MMP-9 were co-localized in parental and MMP-26 sense-transfected ARCaP cells. Moreover, MMP-26 and MMP-9 proteins were both expressed in the same human prostate carcinoma tissue samples examined. These results indicate that MMP-26 may be a physiological and pathological activator of pro-MMP-9.

Publication types

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

MeSH terms

  • Cell Movement / drug effects
  • Collagen Type IV / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Precursors / metabolism*
  • Fibronectins / metabolism
  • Gelatinases / metabolism*
  • Humans
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / pharmacology
  • Matrix Metalloproteinases / physiology*
  • Matrix Metalloproteinases, Secreted
  • Metalloendopeptidases / metabolism*
  • Neoplasm Invasiveness / pathology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured


  • Collagen Type IV
  • Enzyme Precursors
  • Fibronectins
  • Oligodeoxyribonucleotides, Antisense
  • Gelatinases
  • MMP26 protein, human
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Secreted
  • Metalloendopeptidases
  • progelatinase