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Role of decorin in the antimyeloma effects of osteoblasts

Xin Li1, Angela Pennisi, Shmuel Yaccoby

  • 1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Blood
|April 26, 2008
PubMed

Insights

Decorin, a protein from bone-forming osteoblasts, directly inhibits myeloma cell growth and survival. Increasing decorin levels may offer a new strategy for controlling multiple myeloma bone disease.

Area of Science:

  • Biochemistry
  • Oncology
  • Bone Biology

Background:

  • Osteoblasts and bone formation negatively impact myeloma cell growth.
  • Decorin is a key small leucine-rich proteoglycan (SLRP) produced by osteoblasts.

Purpose of the Study:

  • Investigate decorin's role in the antimyeloma effects of osteoblasts.
  • Determine decorin's direct and indirect mechanisms against myeloma cells.

Main Methods:

  • Coculture experiments with osteoblasts, myeloma cells, and osteoclasts.
  • Short-hairpin RNA knockdown and overexpression of decorin.
  • Use of decorin-neutralizing antibodies and recombinant decorin.

Main Results:

  • Decorin knockdown in osteoblasts increased myeloma cell survival.
  • Decorin inhibited osteoclast-supported myeloma cell survival.
  • Decorin induced myeloma cell apoptosis, activated p21(WAF), and inhibited angiogenesis and osteoclastogenesis.

Conclusions:

  • Decorin mediates osteoblast's antimyeloma effects.
  • Decorin directly induces apoptosis and inhibits key processes supporting myeloma.
  • Enhancing SLRPs like decorin could be a therapeutic strategy for multiple myeloma.

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