Rapid normal fibroblast‐tumor crosstalk promotes cancer‐associated fibroblast‐like activation and attenuates mitomycin C cytotoxicity in bladder cancer
In vitro and transcriptomic study reveals rapid fibroblast-tumor crosstalk in early bladder cancer, indicating stromal remodeling dampens mitomycin C cytotoxicity.
Key Points
To determine whether normal fibroblasts actively drive early bladder cancer microenvironmental remodeling and modulate sensitivity to intravesical mitomycin C chemotherapy.
Analyzed transcriptomic profiles of early-stage non-muscle-invasive bladder cancer cohorts across Ta and T1 stages and risk groups.
Assessed bladder cancer cell motility, proliferation, and cadherin expression following culture in normal fibroblast-conditioned medium.
Evaluated normal fibroblast activation markers (α-SMA, FAP, PDGFRβ) within 48 hours of tumor signaling and measured mitomycin C cytotoxicity across varying fibroblast-to-tumor ratios.
Fibroblast-associated transcriptomic scores were significantly higher in T1 than Ta tumors, enriched in high-risk disease, and correlated with epithelial-mesenchymal transition and drug-resistance gene signatures.
Fibroblast-conditioned medium induced EMT-like remodeling (decreased E-cadherin, increased N-cadherin) while reducing proliferation and accelerating cell migration.
Tumor-derived signals rapidly induced CAF-like marker expression in normal fibroblasts within 48 hours, and higher fibroblast-to-tumor ratios progressively attenuated mitomycin C cytotoxicity.