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- Title
Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts.
- Authors
Muller, Joséphine; Duray, Elodie; Lejeune, Margaux; Dubois, Sophie; Plougonven, Erwan; Léonard, Angélique; Storti, Paola; Giuliani, Nicola; Cohen-Solal, Martine; Hempel, Ute; Thijssen, Victor L.; Beguin, Yves; Heusschen, Roy; Caers, Jo
- 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.
- Subjects
PROTEIN metabolism; ANIMAL experimentation; CELL culture; CHROMOSOME abnormalities; GENE expression; MACROPHAGES; MICE; MICROSCOPY; MULTIPLE myeloma; BONE density; MICROARRAY technology; IN vivo studies
- Publication
Cancers, 2019, Vol 11, Issue 2, p261
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11020261