MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL

Conor C. Lynch, Atsuya Hikosaka, Heath B. Acuff, Michelle D. Martin, Noriyasu Kawai, Rakesh K. Singh, Tracy C. Vargo-Gogola, Jennifer L. Begtrup, Todd E. Peterson, Barbara Fingleton, Tomoyuki Shirai, Lynn M. Matrisian, Mitsuru Futakuchi

Research output: Contribution to journalArticlepeer-review

330 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)485-496
Number of pages12
JournalCancer Cell
Volume7
Issue number5
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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