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 t...

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Autores principales:	Sam W. Z. Olechnowicz, Megan M. Weivoda, Seint T. Lwin, Szi K. Leung, Sarah Gooding, Guido Nador, Muhammed Kassim Javaid, Karthik Ramasamy, Srinivasa R. Rao, James R. Edwards, Claire M. Edwards
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8afcd0e1a894dd9a3e3bba9c52aefc9
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spelling	oai:doaj.org-article:d8afcd0e1a894dd9a3e3bba9c52aefc92021-12-02T15:08:21ZMultiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment10.1038/s41598-019-50591-52045-2322https://doaj.org/article/d8afcd0e1a894dd9a3e3bba9c52aefc92019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50591-5https://doaj.org/toc/2045-2322Abstract 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.Sam W. Z. OlechnowiczMegan M. WeivodaSeint T. LwinSzi K. LeungSarah GoodingGuido NadorMuhammed Kassim JavaidKarthik RamasamySrinivasa R. RaoJames R. EdwardsClaire M. EdwardsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sam W. Z. Olechnowicz Megan M. Weivoda Seint T. Lwin Szi K. Leung Sarah Gooding Guido Nador Muhammed Kassim Javaid Karthik Ramasamy Srinivasa R. Rao James R. Edwards Claire M. Edwards Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
description	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.
format	article
author	Sam W. Z. Olechnowicz Megan M. Weivoda Seint T. Lwin Szi K. Leung Sarah Gooding Guido Nador Muhammed Kassim Javaid Karthik Ramasamy Srinivasa R. Rao James R. Edwards Claire M. Edwards
author_facet	Sam W. Z. Olechnowicz Megan M. Weivoda Seint T. Lwin Szi K. Leung Sarah Gooding Guido Nador Muhammed Kassim Javaid Karthik Ramasamy Srinivasa R. Rao James R. Edwards Claire M. Edwards
author_sort	Sam W. Z. Olechnowicz
title	Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
title_short	Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
title_full	Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
title_fullStr	Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
title_full_unstemmed	Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
title_sort	multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d8afcd0e1a894dd9a3e3bba9c52aefc9
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Multiple myeloma increases nerve growth factor and other pain-related markers through interactions with the bone microenvironment

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