Serum galectin-1 in patients with multiple myeloma: associations with survival, angiogenesis, and biomarkers of macrophage activation

Abstract

Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM). We measured serum Gal-1 levels in samples from patients with treatment demanding MM at the time of diagnosis (n=102) and after treatment (n=24) and examined associations of serum Gal-1 with clinicopathological information obtained from patient medical records, as well as data on bone marrow angiogenesis and the macrophage activation biomarkers soluble CD163 (sCD163) and soluble mannose receptor. Serum Gal-1 levels were not elevated in patients with MM at diagnosis compared with healthy donors (median values 8.48 vs 11.93 ng/mL, P=0.05), which is in contrast to results in cHL and CLL. Furthermore, Gal-1 levels did not show association with bone marrow angiogenesis, clinicopathological parameters, overall survival, or response to treatment. There was a statically significant association between Gal-1 and sCD163 levels (R=0.24, P=0.02), but not with soluble mannose receptor (P=0.92). In conclusion, our results indicate that Gal-1 is not an important serum biomarker in MM, which is in contrast to data from patients with cHL and CLL. However, the association with sCD163 is in line with previous data showing that Gal-1 may be involved in alternative (M2-like) activation of macrophages.

Galectins: Multitask signaling molecules linking fibroblast, endothelial and immune cell programs in the tumor microenvironment

“…Recently, Van Woensel and coworkers showed that intranasal delivery of Gal-1 siRNA induced a remarkable switch in the TME composition, reducing macrophage polarization from M1 to M2 and inhibiting recruitment of monocytic MDSCs during glioblastoma multiforme progression [122]. In this sense, Gal-1 levels positively correlated with soluble CD163, a biomarker of M2 macrophage activation in sera from multiple myeloma patients [123].…”

Role of Galectins in Multiple Myeloma

“…Moreover, analyses of gene expression datasets of MM primary CD138+ cells revealed that LGALS1 (galectin-1 gene) levels are significantly higher in newly diagnosed MM (MMD) patients, but not in MGUS, SMM and MM relapsed, compared to healthy donors [ 24 , 107 ]. Recently, it has been published that, in peripheral blood sera, galectin-1 protein level was borderline significantly higher in MMD compared to healthy controls and that the levels of this lectin in peripheral blood are not associated with OS, response to treatment and clinical pathological parameters [ 108 ]; on the other hand, this study shows only a positive correlation between galectin-1 and soluble (s)CD163, a macrophage activation marker, and sCD138 [ 108 ]. Moreover, galectin-1 has been identified as a ECM-associated protein that characterizes only the MM BM and not the ECM of MGUS patients or healthy controls [ 107 ].…”

Prognostic Value of Galectin-9 Relates to Programmed Death-Ligand 1 in Patients With Multiple Myeloma

“…The prognostic roles of galectin family members have also been studied in multiple myeloma. A previous study reported no increase in the serum LGALS1 level in multiple myeloma and no association with its prognosis (20). However, another study reported that LGALS1 expression in multiple myeloma cells was upregulated under hypoxic conditions and that downregulation significantly reduced the tumor burden in a mouse model (21).…”