@article{3d0be9abc4944e66a315ecf6b8739714,
title = "Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment",
abstract = "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.",
author = "Olechnowicz, {Sam W.Z.} and Weivoda, {Megan M.} and Lwin, {Seint T.} and Leung, {Szi K.} and Sarah Gooding and Guido Nador and Javaid, {Muhammed Kassim} and Karthik Ramasamy and Rao, {Srinivasa R.} and Edwards, {James R.} and Edwards, {Claire M.}",
note = "Funding Information: We thank the patients who donated clinical samples used in this research and M. Sultanova and C. Everett for assistance in obtaining patient samples and data. We acknowledge the contribution to this study made by the OxfordCentre for Histopathology Research and the Oxford Radcliffe Biobank, which are supported by theNIHR Oxford Biomedical Research Centre. This work was funded by Orthopaedic Research UK (C.E.), Bloodwise (C.E.), Arthritis Research UK (J.E.) a Wellcome Trust Research Training Fellowship 2013-2016 (SG) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funding bodies have had no roles in the design of the study, collection, analysis, and interpretation of data or in writing the manuscript. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-50591-5",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}