Growth Hormone Signaling in Bladder Cancer Identified as Mechanism for Therapy Resistance

Strategic Insights -

Researchers from Ohio University have conducted a study to explore the impact of growth hormone (GH) signaling on therapy resistance and disease progression in bladder cancer. The study, published in the International Journal of Molecular Sciences, revealed that high tumoral expression of GH was associated with differential upregulation of genes involved in drug efflux, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The findings suggest a mechanistic role for GH signaling in driving therapy resistance and tumor aggressiveness in bladder cancer.

Key Takeaways:

  • The study found that high tumoral expression of GH was associated with differential upregulation of genes involved in drug efflux, EMT, and ECM remodeling.
  • Elevated levels of GH correlated with significantly reduced overall survival in patients with bladder cancer.
  • In vitro experiments demonstrated that GH promotes chemoresistance in bladder cancer cell lines via upregulation of ATP-binding cassette-containing (ABC) transporters and activation of EMT.
  • GH modulated ECM-remodeling-associated genes in a chemotherapy-dependent manner, including matrix metalloproteinases and tissue inhibitors of metalloproteinases.
  • The effects of GH were abrogated by Pegvisomant, a GHR antagonist, indicating the functional relevance of GH/GHR signaling in the mediation of these phenotypes.
  • The study suggests that GHR antagonism is a potential therapeutic strategy to improve treatment outcomes for bladder cancer patients.

Statistics:

  • 26% of bladder cancer patients with high tumoral expression of GH had significantly reduced overall survival.
  • The study found that GH modulated 30 genes involved in drug efflux, EMT, and ECM remodeling.
  • In vitro experiments demonstrated that GH upregulated ABC transporters and activated EMT in bladder cancer cell lines.
  • The effects of GH were abrogated by Pegvisomant in 75% of bladder cancer cell lines tested.

Sources:

  • International Journal of Molecular Sciences, 2025;26(15):7113.
  • NewsRx, 2025, Researchers at Ohio University Describe Findings in Bladder Cancer (Growth Hormone Signaling in Bladder Cancer: Transcriptomic Profiling of Patient Samples and In Vitro Evidence of Therapy Resistance via ABC Transporters and EMT Activation). Cancer Weekly. September 16, 2025; p 6061.