MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. 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, Department of Cancer Biology, Vanderbilt University, Nashville, TN

Jennifer J. Westendorf, Luke Hoeppner

Research output: Contribution to journalShort surveypeer-review

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)
Number of pages1
JournalUrologic Oncology: Seminars and Original Investigations
Volume25
Issue number2
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

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