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Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
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Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone

Sam W Z Olechnowicz1,2,3, Megan M Weivoda2, Seint T Lwin1,2

  • 1Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Scientific Reports
|October 4, 2019
PubMed

Insights

Multiple myeloma (MM) induces nerve growth factor (NGF) in the bone microenvironment, contributing to pain. Adiponectin-based therapies can suppress this NGF induction, offering a new avenue for pain management.

Area of Science:

  • Oncology
  • Neuroscience
  • Biochemistry

Background:

  • Interactions between multiple myeloma (MM) and bone marrow (BM) support tumor growth.
  • The cellular mechanisms of pain in MM are not well understood.

Purpose of the Study:

  • To investigate the cellular mechanisms underlying pain in multiple myeloma.
  • To identify novel therapeutic targets for pain management in MM.

Main Methods:

  • In vivo murine models of MM were utilized.
  • Expression of nerve growth factor (NGF) and related pain markers were analyzed.
  • The effects of adiponectin-directed therapeutics and NF-κB signaling inhibitors were evaluated.

Main Results:

  • Significant induction of NGF by the tumor-bearing bone microenvironment was observed.
  • Osteoblasts, not MM cells, expressed and upregulated NGF in response to MM cells or TNF-α.
  • Adiponectin-directed therapeutics (AdipoRON, L-4F) and BMS-345541 suppressed TNF-α-mediated NGF induction.

Conclusions:

  • Cellular interactions in the MM-bone microenvironment promote pain-related properties via NGF induction.
  • Adiponectin-based therapies and NF-κB inhibitors show potential for developing novel analgesics for MM-related pain.

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