Fig. 6

Tumor-associated MSCs source to bone remodeling of ccRCC bone metastasis. A Overview of number of significant ligand receptor pairs (Additional file 1: Table S6). B Bubble heatmap showing expression of ligand (left: tumor cells and stromal cell subsets) and receptor (right: stromal and myeloid subsets) pairs in different stromal and immune subsets. Dot size indicates expression ratio; colored represents average gene expression. C Circle plots showing the inferred RANKL-RANK signaling between MSC-2 and osteoclasts. D Box plot showing RANKL expression in MSC-2 and OPG expression in MSC-1 (Benign n = 8; Bone Met n = 7). Average gene expression was used, each dot represents a sample. Significance was assessed using two-sided Wilcoxon rank sum test (*p < 0.05, **p < 0.01). E Bar plot showing relative mRNA expression (log fold change) of RANKL in Benign (n = 5) and Bone Met (n = 7) tissue by RT-qPCR. Data are expressed using the 2 − ∆∆Ct method. Gene expression levels were normalized to the benign control. Statistical significance determined using two-sided t-test. F Immunostaining in tissue from bone metastatic ccRCC stained for RANKL, MSC-2 specific marker CD90, and DAPI. G Schematic illustration of MSC cell shift in mediating RANKL/OPG-RANK signaling pathway. For box plots, center line represents the median and box limits represent upper and lower quartiles, and whiskers depict 1.5 × the interquartile range (IQR)