Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, Vargo-Gogola TC, Begtrup JL, Peterson TE, Fingleton B, Shirai T, Matrisian LM, Futakuchi M
Cancer Cell. 2005 7 (5)
We developed a rodent model that mimics the osteoblastic and osteolytic changes associated with human metastatic prostate cancer. Microarray analysis identified MMP-7, cathepsin-K, and apolipoprotein D as being upregulated at the tumor-bone interface. MMP-7, which was produced by osteoclasts at the tumor-bone interface, was capable of processing RANKL to a soluble form that promoted osteoclast activation. MMP-7-deficient mice demonstrated reduced prostate tumor-induced osteolysis and RANKL processing. This study suggests that inhibition of MMP-7 will have therapeutic benefit in the treatment of prostate cancer-induced osteolysis.
MeSH Terms (33)Acid Phosphatase Actins Animals Carrier Proteins Disease Models, Animal Down-Regulation Gene Expression Gene Expression Profiling Glycoproteins Humans Isoenzymes Male Matrix Metalloproteinase 7 Membrane Glycoproteins Mice Mice, Inbred C57BL Mice, Knockout Models, Biological Monocytes Osteoclasts Osteolysis Osteoprotegerin Parathyroid Hormone-Related Protein Prostatic Neoplasms RANK Ligand Rats Rats, Inbred F344 Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear Receptors, Tumor Necrosis Factor Skull Tartrate-Resistant Acid Phosphatase Up-Regulation