Heterogeneous activation of MMP-9 due to prostate cancer-bone interaction.

OBJECTIVES 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 Ac…