title: Heterogeneous activation of MMP-9 due to prostate cancer-bone interaction.
abstract: OBJECTIVE
  To determine whether matrix metalloproteinase (MMP)-9 activation resulting from prostate cancer cell-bone interaction is dependent on the tumor cell type and/or the nature of the bone microenvironment.
  
  
  METHODS
  In vitro co-cultures of human prostate cancer cells (PC3 and C4-2B) and mouse, human fetal, or human adult tissues were performed. In vivo the tumor cells were intratibially injected in SCID mice or intraosseously inoculated into fetal or adult bone xenografts in SCID mice. MMP-2 and MMP-9 expression and activation were determined by gelatin zymography in conditioned media obtained in vitro and in lysates derived from the in vivo studies at different time points.
  
  
  RESULTS
  Activation of MMP-9 occurred when PC3 cells interacted with human adult or fetal bone, either in vitro or in vivo at early time points. With C4-2B cells, activation of MMP-9 only happened in the human adult bone microenvironment at early time points after intraosseous inoculation of tumor cells. No activation of MMP-9 occurred when PC3 or C4-2B cells interacted with mouse bone, either in vitro or in vivo.
  
  
  CONCLUSIONS
  The results of our study have shown that the activation of MMP-9 when human prostate cancer cells interact with bone depends on the particular identity of the tumor cells and the type of bone tissue used. These findings have broad implications for experimental models attempting to define tumor-microenvironmental interactions in bone metastasis.
authors: Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors: Christoph
authors: C
authors: Wiesner
authors: R Daniel
authors: RD
authors: Bonfil
authors: Zhong
authors: Z
authors: Dong
authors: Hamilto
authors: H
authors: Yamamoto
authors: Sanaa M
authors: SM
authors: Nabha
authors: Hong
authors: H
authors: Meng
authors: Allen
authors: A
authors: Saliganan
authors: Aaron
authors: A
authors: Sabbota
authors: Michael L
authors: ML
authors: Cher
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology* / Q000201:enzymology*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*
chemical_list: D020780:Matrix Metalloproteinase 9