Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts
AbstractMultiple 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
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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.
Muller J, Duray E, Lejeune M, Dubois S, Plougonven E, Léonard A, Storti P, Giuliani N, Cohen-Solal M, Hempel U, Thijssen VL, Beguin Y, Heusschen R, Caers J. Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts. Cancers. 2019; 11(2):261.Chicago/Turabian Style
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. 2019. "Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts." Cancers 11, no. 2: 261.
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