Apo2L/TRAIL inhibits tumor growth and bone destruction in a murine model of multiple myeloma

Agatha Labrinidis1, Peter Diamond, Sally Martin

  • 1Discipline of Orthopaedics and Trauma, The University of Adelaide, Royal Adelaide Hospital, and Hanson Institute, South Australia, Australia.

Abstract

Insights

Recombinant soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively reduced multiple myeloma tumor burden and protected against bone destruction in a mouse model. This suggests TRAIL is a promising therapeutic for multiple myeloma patients.

Area of Science:

  • Oncology
  • Bone Biology
  • Apoptosis Signaling

Background:

  • Multiple myeloma is an incurable hematologic malignancy.
  • Therapeutic strategies are needed to combat tumor progression and bone destruction.
  • Recombinant soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent.

Purpose of the Study:

  • To investigate the efficacy of recombinant soluble Apo2L/TRAIL in inhibiting tumor progression and bone destruction in a xenogeneic multiple myeloma model.
  • To assess the impact of Apo2L/TRAIL on myeloma burden within the bone microenvironment.

Main Methods:

  • A xenogeneic mouse model of multiple myeloma was established using Apo2L/TRAIL-sensitive human myeloma cells (RPMI-8226 or KMS-11) xenografted into the tibial marrow cavity of nude mice.
  • Tumor burden was monitored using bioluminescence imaging.
  • Myeloma-induced osteolysis was quantified using in vivo micro-computed tomography.

Main Results:

  • Transplanted myeloma cells progressively increased tumor burden and caused extensive osteolysis in the bone marrow.
  • Treatment with recombinant soluble Apo2L/TRAIL significantly reduced myeloma burden in the bone marrow.
  • Apo2L/TRAIL treatment conferred significant protection against myeloma-induced osteolysis, mediated by direct apoptosis of myeloma cells.

Conclusions:

  • This study provides the first in vivo evidence of recombinant soluble Apo2L/TRAIL's efficacy against multiple myeloma burden and associated bone destruction within the bone microenvironment.
  • The findings support the direct apoptotic action of Apo2L/TRAIL on myeloma cells in vivo.
  • Recombinant soluble Apo2L/TRAIL warrants clinical evaluation for patients with multiple myeloma.