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Cancers 2019, 11(2), 261;

Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts

Laboratory of Hematology, GIGA-Research, University of Liège, 4000 Liège, Belgium
Department of Chemical Engineering, University of Liège, 4000 Liège, Belgium
Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
Department of Rheumatology, Hôpital Lariboisière, INSERM-UMR 606, Université Paris Diderot, 75010 Paris, France
Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology & Radiation Oncology, 1081 Amsterdam, The Netherlands
Department of Medicine, Division of Hematology, University and CHU of Liège, 4000 Liège, Belgium
Author to whom correspondence should be addressed.
Both authors contributed equally.
Received: 23 December 2018 / Revised: 15 February 2019 / Accepted: 17 February 2019 / Published: 23 February 2019
PDF [3036 KB, uploaded 25 February 2019]


Multiple myeloma osteolytic disease is caused by an uncoupled bone-remodelling process with an increased osteoclast activity. Disease development relies on interactions between myeloma cells and bone marrow stromal cells. Recent findings suggest a role for glycan-binding proteins in myeloma microenvironment. Here, we investigated lectins involved in osteoclastogenesis and their role in myeloma bone disease. Microarray data analysis showed a lower expression of galectin-1 (gal-1) in mature osteoclasts compared to monocytic progenitor cells, confirmed at the RNA and protein levels in osteoclast cultures. Confocal microscopy showed that gal-1 localised predominantly in the sealing zone of mature osteoclasts. Although equal differentiated-osteoclast numbers, gal-1−/− osteoclasts showed a higher resorption activity compared to wild-type controls. Micro-computed tomography showed an aberrant bone phenotype with decreased bone densities in gal-1−/− mice. In vivo, tumour progression was faster in gal-1−/− mice and associated with a marked bone loss. Additionally, myeloma cells were found to decrease gal-1 expression in osteoclasts. Our results demonstrate that galectin-1 regulates osteoclast activity with an increased resorption by gal-1−/− osteoclasts and decreased bone densities in gal-1−/− mice. We observed an enhanced tumour development in gal-1−/− mice compared to wild-type mice, suggesting that galectin-1 has a functional role in stromal cells in myeloma microenvironment. View Full-Text
Keywords: multiple myeloma; osteolytic disease; galectin-1; osteoclasts; tumour microenvironment multiple myeloma; osteolytic disease; galectin-1; osteoclasts; tumour microenvironment

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Muller, J.; Duray, E.; Lejeune, M.; Dubois, S.; Plougonven, E.; Léonard, A.; Storti, P.; Giuliani, N.; Cohen-Solal, M.; Hempel, U.; Thijssen, V.L.; Beguin, Y.; Heusschen, R.; Caers, J. Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts. Cancers 2019, 11, 261.

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