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

Joséphine Muller, Elodie Duray, Margaux Lejeune, Sophie Dubois, Erwan Plougonven, Angélique Léonard, Paola Storti, Nicola Giuliani, Martine Cohen-Solal, Ute Hempel, Victor L. Thijssen, Yves Beguin, Roy Heusschen, Jo Caers

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Article number261
JournalCancers
Volume11
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Cite this

Muller, J., Duray, E., Lejeune, M., Dubois, S., Plougonven, E., Léonard, A., ... Caers, J. (2019). Loss of stromal galectin-1 enhances multiple myeloma development: Emphasis on a role in osteoclasts. Cancers, 11(2), [261]. https://doi.org/10.3390/cancers11020261