The reactive stroma microenvironment and prostate cancer progression.

Area of Science:

• Oncology
• Cancer Biology
• Prostate Cancer Research

Background:

• Reactive stroma plays a critical role in prostate cancer initiation and progression.
• Key markers of reactive stroma are known, but its origins and regulatory mechanisms remain unclear.
• The biology of reactive stroma in cancer parallels stromal responses observed during wound healing.

Purpose of the Study:

• To investigate the stem/progenitor cells of origin for reactive stroma in prostate cancer.
• To elucidate the mechanisms regulating the recruitment and activation of stromal cells into myofibroblasts or carcinoma-associated fibroblasts.
• To identify key regulatory factors involved in reactive stroma formation and function.

Main Methods:

• Analysis of key regulatory factors including transforming growth factor β, interleukin-8, fibroblast growth factors, connective tissue growth factor, wingless homologs-Wnts, and stromal cell-derived factor-1.
• Comparative studies of reactive stroma biology in cancer and wound repair.
• Investigation of reactive stroma-carcinoma interactions.

Main Results:

• Reactive stroma emerges early in prostate cancer and coevolves with tumor progression.
• Several key regulatory factors (TGF-β, IL-8, FGFs, CTGF, Wnts, SDF-1) are implicated in reactive stroma biology.
• The interactions between reactive stroma and carcinoma cells influence cancer progression and metastasis.

Conclusions:

• Understanding the origins and regulatory mechanisms of reactive stroma is essential for developing novel prostate cancer therapies.
• Targeting the reactive stroma niche offers a promising strategy to inhibit prostate cancer progression and metastasis.
• Decoupling the reactive stroma niche represents a potential therapeutic approach to uncouple cancer progression.