RANK (receptor activator of nuclear factor-κB) and RANKL expression in multiple myeloma.
Open accessAbstract
Summary. The new members of the tumour necrosis factor (TNF) receptor‐ligand family, receptor activator of nuclear factor‐κB ligand (RANKL) and its receptor RANK, play a crucial role in osteoclast differentiation and activation. An increased expression of RANKL and/or RANK may be involved in the excessive bone resorption observed in multiple myeloma (MM). We used immunohistochemistry to study RANK and RANKL expression in bone marrow (BM) biopsies obtained at diagnosis in 15 MM patients, six patients with monoclonal gammopathy of undetermined significance (MGUS) and 10 normal BM biopsies. Plasma cells were not labelled with anti‐RANKL or anti‐RANK antibodies. In all biopsies, RANKL was expressed in endosteal bone surface, around vessels and in cells characterized by cytoplasmic expansions. These last cells did not express CD45 and were vimentin positive, corresponding to bone marrow stromal cells. Numerous stromal cells expressed RANKL in MM and MGUS specimens, with a greater expression in MM than in MGUS. Very few cells were stained with anti‐RANKL in normal BM specimens. With the anti‐RANK antibody, small mononuclear cells in the bone microenvironment were positive and were identified as erythroblast cells. In conclusion, we showed that RANKL was expressed in reticular stromal cells, with a greater intensity in myeloma specimens. These results suggest that RANKL overexpressed by bone marrow stromal cells may contribute to the high rate of bone resorption observed in MM.
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Prostate cancer cells and multiple myeloma cells express RANKL directly.
“prostate cancer cells (CaP) (314 -316) and MM cells (317-322) have been shown to express RANKL directly.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [319]
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- Authors
- Roux, S., Meignin, V., Quillard, J., Meduri, G., Guiochon‐Mantel, A., Fermand, J., Milgrom, E., & Mariette, X.
- Affiliations
- Inserm (FR)
- Hôpital Saint-Louis (FR)
- Bicêtre Hospital (FR)
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2002-03-25
- Volume
- 117
- Issue
- 1
- Pages
- 86-92
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W2074110200
- Cited by
- 125
- References
- 27
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- RANK, RANKL, multiple myeloma, monoclonal gammopathy of undetermined significance, mesenchymal stem cells, bone resorption, osteoclastogenesis, erythroblasts
- MeSH terms
- Bone Marrow Cells, Carrier Proteins, Glycoproteins, Humans, Immunohistochemistry, Membrane Glycoproteins, Multiple Myeloma, Paraproteinemias, Case-Control Studies, Stromal Cells, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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