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 Vargo-Gogola, Jennifer L. Begtrup, Todd E. Peterson, Barbara Fingleton, Tomoyuki Shirai, Lynn M. Matrisian, Mitsuru Futakuchi

Research output: Contribution to journalArticle

250 Citations (Scopus)

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
Externally publishedYes

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Osteolysis
Matrix Metalloproteinases
Prostatic Neoplasms
Osteoclasts
Apolipoproteins D
Cathepsin K
Bone and Bones
Neoplasms
Cathepsin D
Microarray Analysis
Prostate
Rodentia
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Lynch, C. C., Hikosaka, A., Acuff, H. B., Martin, M. D., Kawai, N., Singh, R. K., ... Futakuchi, M. (2005). MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell, 7(5), 485-496. https://doi.org/10.1016/j.ccr.2005.04.013

MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. / Lynch, Conor C.; Hikosaka, Atsuya; Acuff, Heath B.; Martin, Michelle D.; Kawai, Noriyasu; Singh, Rakesh K.; Vargo-Gogola, Tracy; Begtrup, Jennifer L.; Peterson, Todd E.; Fingleton, Barbara; Shirai, Tomoyuki; Matrisian, Lynn M.; Futakuchi, Mitsuru.

In: Cancer Cell, Vol. 7, No. 5, 05.2005, p. 485-496.

Research output: Contribution to journalArticle

Lynch, CC, Hikosaka, A, Acuff, HB, Martin, MD, Kawai, N, Singh, RK, Vargo-Gogola, T, Begtrup, JL, Peterson, TE, Fingleton, B, Shirai, T, Matrisian, LM & Futakuchi, M 2005, 'MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL', Cancer Cell, vol. 7, no. 5, pp. 485-496. https://doi.org/10.1016/j.ccr.2005.04.013
Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK et al. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell. 2005 May;7(5):485-496. https://doi.org/10.1016/j.ccr.2005.04.013
Lynch, Conor C. ; Hikosaka, Atsuya ; Acuff, Heath B. ; Martin, Michelle D. ; Kawai, Noriyasu ; Singh, Rakesh K. ; Vargo-Gogola, Tracy ; Begtrup, Jennifer L. ; Peterson, Todd E. ; Fingleton, Barbara ; Shirai, Tomoyuki ; Matrisian, Lynn M. ; Futakuchi, Mitsuru. / MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. In: Cancer Cell. 2005 ; Vol. 7, No. 5. pp. 485-496.
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