Heterogeneous activation of MMP-9 due to prostate cancer-bone interaction.
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.
Wiesner
Christoph
C
Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Bonfil
R Daniel
RD
Dong
Zhong
Z
Yamamoto
Hamilto
H
Nabha
Sanaa M
SM
Meng
Hong
H
Saliganan
Allen
A
Sabbota
Aaron
A
Cher
Michael L
ML
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*
D020780:Matrix Metalloproteinase 9