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Receptor-Activator of Nuclear KappaB Ligand Expression as a New Therapeutic Target in Primary Bone Tumors

Tetsuro Yamagishi1, Hiroyuki Kawashima1, Akira Ogose2

  • 1Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Plos One
|May 11, 2016
PubMed

Insights

Receptor-activator of nuclear kappaB ligand (RANKL) is highly expressed in giant cell tumors of bone and other primary bone tumors, suggesting denosumab as a potential therapy for these conditions.

Area of Science:

  • Oncology
  • Orthopedics
  • Molecular Biology

Background:

  • The receptor-activator of nuclear kappaB ligand (RANKL) pathway is crucial for osteoclast formation and bone resorption.
  • Denosumab, an anti-RANKL antibody, is approved for multiple myeloma, bone metastases, and giant cell tumor of bone.
  • Quantitative data on RANKL expression across diverse bone tumor types is lacking.

Purpose of the Study:

  • To quantitatively compare RANKL mRNA expression in various primary and metastatic bone tumors.
  • To investigate the potential of bone tumors expressing RANKL as therapeutic targets for denosumab.

Main Methods:

  • Real-time PCR was used to analyze RANKL mRNA expression in 135 clinical bone tumor specimens.
  • RPMI8226 cell line served as a reference for RANKL expression normalization.
  • Immunohistochemistry was performed on 64 cases to evaluate RANKL protein expression.

Main Results:

  • Giant cell tumor of bone exhibited the highest RANKL expression and RANKL/osteoprotegerin ratio.
  • Elevated RANKL mRNA levels were found in aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma.
  • RANKL-positive stromal cells were identified in giant cell tumor of bone and fibrous dysplasia.

Conclusions:

  • Certain primary bone tumors, particularly those with high RANKL expression, represent potential new therapeutic targets for denosumab.
  • Targeting the RANKL pathway may be beneficial for bone tumors involving osteoclast-mediated resorption.

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