Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment.
Sam W Z OlechnowiczMegan M WeivodaSeint T LwinSzi K LeungSarah GoodingGuido NadorMuhammed Kassim JavaidKarthik RamasamySrinivasa R RaoJames R EdwardsClaire M EdwardsPublished in: Scientific reports (2019)
Interactions between multiple myeloma (MM) and bone marrow (BM) are well documented to support tumour growth, yet the cellular mechanisms underlying pain in MM are poorly understood. We have used in vivo murine models of MM to show significant induction of nerve growth factor (NGF) by the tumour-bearing bone microenvironment, alongside other known pain-related characteristics such as spinal glial cell activation and reduced locomotion. NGF was not expressed by MM cells, yet bone stromal cells such as osteoblasts expressed and upregulated NGF when cultured with MM cells, or MM-related factors such as TNF-α. Adiponectin is a known MM-suppressive BM-derived factor, and we show that TNF-α-mediated NGF induction is suppressed by adiponectin-directed therapeutics such as AdipoRON and L-4F, as well as NF-κB signalling inhibitor BMS-345541. Our study reveals a further mechanism by which cellular interactions within the tumour-bone microenvironment contribute to disease, by promoting pain-related properties, and suggests a novel direction for analgesic development.
Keyphrases
- growth factor
- neuropathic pain
- chronic pain
- pain management
- multiple myeloma
- bone mineral density
- induced apoptosis
- bone marrow
- stem cells
- rheumatoid arthritis
- spinal cord
- bone loss
- soft tissue
- metabolic syndrome
- cell cycle arrest
- signaling pathway
- spinal cord injury
- insulin resistance
- mesenchymal stem cells
- type diabetes
- single cell
- small molecule
- pi k akt
- endoplasmic reticulum stress
- endothelial cells
- body composition
- cell death
- inflammatory response