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Cancers 2019, 11(2), 261; https://doi.org/10.3390/cancers11020261

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

1
Laboratory of Hematology, GIGA-Research, University of Liège, 4000 Liège, Belgium
2
Department of Chemical Engineering, University of Liège, 4000 Liège, Belgium
3
Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
4
Department of Rheumatology, Hôpital Lariboisière, INSERM-UMR 606, Université Paris Diderot, 75010 Paris, France
5
Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
6
Amsterdam UMC, Vrije Universiteit Amsterdam, Medical Oncology & Radiation Oncology, 1081 Amsterdam, The Netherlands
7
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
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Abstract

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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