Fig. 1

GPER1 is upregulated in WM, and its pharmacological activation triggers in vitro and in vivo anti-tumor activity. A RNA-seq analysis of GPER1 mRNA expression in CD19 + cells from WM patients (n = 72) and healthy donor (HD)-derived B cells. These latter included CD19 + /CD27 + B cells (n = 9), CD19 + /CD27 + B cells (n = 9) and CD138 + plasma cells (n = 16). B RNA-seq analysis of GPER1 mRNA expression in WM patients carrying MYD88-WT (n = 20) or MYD88-MUT (n = 52), with the latter further divided into CXCR4-WT (n = 32) or CXCR4-MUT (n = 20). C IHC analysis of GPER1 performed in lymph node specimens from WM patients (n = 4) and normal lymph nodes (n = 2), (20× magnification). D Cell viability was assessed by CTG assay 72 h after treatment with G-1 at the indicated doses. E A colony assay was performed in methylcellulose using WM cells treated with 1 μM G-1 for 72 h; representative pictures of colonies (10× magnification) are reported. F BCWM-1 cells were transfected with [100 nM] scrambled siRNAs or two different GPER1-targeting siRNAs (siGPER1#1 and siGPER#2), and then treated with G-1 [1 μM] or DMSO. GPER expression and cell viability were assessed 48 h after transfection by WB and CTG respectively. G Cell viability was assessed in primary CD19 + cells by CTG assay 72 h after treatment with G-1 [1 μM] at the indicated doses. H Average and SD of tumor volume (mm3) from groups of mice (n = 5/group) versus time (days) when tumor was measured. BCMW.1 cells (5 × 106 in 100 mL of serum-free RPMI1640 medium) were implanted in the flank of NOD/SCID mice. After tumor detection, mice were randomized to intraperitoneal treatment with G-1 [1 mg/Kg] or vehicle. Data are mean tumor volume ± SD. Arrows represent treatments. I Kaplan–Meier survival plot showing survival for mice treated with vehicle or G-1. *p < 0.05 from a Wilcoxon rank sum test in A, from a pairwise comparison using Wilcoxon rank sum exact test in B, and from Student’s t-test in other panels. **p < 0.05 from a log-rank test