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.

Loss of stromal galectin-1 enhances multiple myeloma development: Emphasis on a role in osteoclasts / 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. - In: CANCERS. - ISSN 2072-6694. - 11:2(2019), p. 261. [10.3390/cancers11020261]

Loss of stromal galectin-1 enhances multiple myeloma development: Emphasis on a role in osteoclasts

Storti, Paola;Giuliani, Nicola;
2019-01-01

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.
2019
Loss of stromal galectin-1 enhances multiple myeloma development: Emphasis on a role in osteoclasts / 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. - In: CANCERS. - ISSN 2072-6694. - 11:2(2019), p. 261. [10.3390/cancers11020261]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2858099
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