Journal: Bioactive Materials
Article Title: Biomimetic bone niche reconstructs proliferation-inhibited and therapy-resistant bone-metastatic prostate cancer
doi: 10.1016/j.bioactmat.2025.09.041
Figure Lengend Snippet: Cell interactions and drug resistance in the 3D-printed BME . a) Schematic illustrating cellular interactions among prostate cancer cells, MSCs, and osteoblasts within the BME. b) Ligand-receptor interaction network among cancer cells, MSCs, and osteoblasts in the BME, identified using the iTALK algorithm. c) Top 20 ligand-receptor pairs between MSCs/osteoblasts and tumor cells in the BME (iTALK analysis). d, e) Comparison of the top 100 ligand-receptor pairs from bulk RNA-seq and single-cell RNA-seq data, highlighting overlapping interactions between MSCs/osteoblasts and tumor cells. f) Schematic and fluorescence images showing tumor spheroids cultured in BME or control (3D-only) conditions under 10 μM enzalutamide treatment; images captured on days 0, 3, 5, and 7. g) Following enzalutamide administration, a quantitative comparison of the relative proliferation (normalized to Day 1) of C4-2B tumor spheroids between the control and BME-treated groups was conducted over time (Days 1, 3, 5, and 7). h) Schematic of flow cytometry sorting and analysis of dissociated tumor cells from BME and control groups, stained for live/dead and apoptosis markers. i, j) Flow cytometry quantification of dead and apoptotic tumor cells in BME and control groups on days 1 and 7 post-enzalutamide treatment. k) KEGG enrichment analysis of DEGs showing altered metabolism-related pathways in BME compared to control. l) GSEA highlighting differences in MYC targets (V1) and fatty acid metabolism pathways between BME and control tumor cells. m) Kaplan-Meier curve showing association of BME-derived gene signatures (bulk RNA-seq) with reduced progression-free survival in TCGA prostate cancer cohort (p = 0.0576). n) Kaplan-Meier curve showing association of distal tumor gene signatures (single-cell RNA-seq) with reduced progression-free survival in TCGA dataset (p = 0.0595). A paired t -test was employed to ascertain significance: ns (not significant), *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, respectively.
Article Snippet: Cell lines and culture: Primary mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from Procell Bioscience Inc. (China).
Techniques: Comparison, RNA Sequencing, Fluorescence, Cell Culture, Control, Flow Cytometry, Staining, Derivative Assay