Role of Galectins in Multiple Myeloma

Abstract

Galectins are a family of lectins that bind β-galactose-containing glycoconjugates and are characterized by carbohydrate-recognition domains (CRDs). Galectins exploit several biological functions, including angiogenesis, regulation of immune cell activities and cell adhesion, in both physiological and pathological processes, as tumor progression. Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by the tight adhesion between tumoral PCs and bone marrow (BM) microenvironment, leading to the increase of PC survival and drug resistance, MM-induced neo-angiogenesis, immunosuppression and osteolytic bone lesions. In this review, we explore the expression profiles and the roles of galectin-1, galectin-3, galectin-8 and galectin-9 in the pathophysiology of MM. We focus on the role of these lectins in the interplay between MM and BM microenvironment cells showing their involvement in MM progression mainly through the regulation of PC survival and MM-induced angiogenesis and osteoclastogenesis. The translational impact of these pre-clinical pieces of evidence is supported by recent data that indicate galectins could be new attractive targets to block MM cell growth in vivo and by the evidence that the expression levels of LGALS1 and LGALS8, genes encoding for galectin-1 and galectin-8 respectively, correlate to MM patients’ survival.

Decoding the sweet regulation of apoptosis: the role of glycosylation and galectins in apoptotic signaling pathways

“…However, the localization of galectins is not restricted to the intracellular compartments [22]. Several secreted galectins such as Gal-1, Gal-3, Gal-4, Gal-8, and Gal-9 are localized on the cell membrane and in the extracellular matrix (ECM) [21,32]. Despite the lack of the signal sequence for a classical secretion, galectins are suggested to be secreted by a non-classical pathway.…”

Classification of Solitary Plasmacytoma, Is it more Intricate than Presently Suggested? A Commentary

“…The involvement of clonal plasma cells with the bone marrow environment may determine also the stage of the SP 7 . More insight may be obtained from similar studies on the PCM with its surroundings 8 - 12 .…”

Galectins in Cancer and Translational Medicine: From Bench to Bedside

“…The cluster worded “Galectins and Cancer”, as expected, is the larger one. The cluster includes several papers focused on cancer diagnosis, prognosis, and galectin-based therapeutic approaches [ 4 , 5 , 6 , 7 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. The implication of galectins in tumor growth and progression, and more in general the impact that these molecules may have in oncology, is very well-known and has been extensively reviewed [ 3 ].…”

“…Advedissian et al [ 19 ] investigated the physiological function of this lectin in epithelial cells and demonstrated its aberrant expression in malignant epithelial counterparts. Studies on the functional role of galectins in neuroblastoma [ 7 ] and multiple myeloma [ 20 ], two relatively rare tumor conditions, are also presented in this special issue. Up-regulation of galectin-1 has been previously reported in aggressive neuroblastoma, the most common extracranial tumor of childhood.…”

“…In this niche, neo-angiogenesis is induced as well as immunosuppression and osteolytic metastasis. In the review by Storti et al [ 20 ], the authors analyze the expression profile of different galectin molecules and their functional activities in these specific tumors, with special focus on tumor progression, angiogenesis, and osteoclastogenesis. Several of the identified galectins may be attractive targets for multiple myeloma therapy.…”