Prostate stromal fibroblast signaling

Prostate stromal fibroblast signaling refers to the complex network of paracrine and autocrine communication between fibroblasts and epithelial cells within the prostate microenvironment (PMID: 26851671). In a healthy prostate, these signals maintain tissue homeostasis; however, in diseases like prostate cancer and benign prostatic hyperplasia (BPH), fibroblasts often transition into an activated state known as cancer-associated fibroblasts (CAFs). These CAFs secrete a variety of growth factors such as TGF-beta, FGF, and HGF, as well as cytokines like CXCL12, which promote tumor growth, invasion, and therapeutic resistance (PMID: 22430213, PMID: 18448482). Key pathways involved in this crosstalk include the Wnt and Hedgehog signaling pathways, which are often dysregulated to favor a pro-tumorigenic environment (PMID: 22941111). Targeting this signaling network involves inhibiting specific ligands or receptors to disrupt the supportive niche provided by the stroma. While therapeutic strategies like TGF-beta or FGFR inhibition are being explored, the complexity and redundancy of these pathways, along with their roles in normal physiology, present significant challenges for clinical safety and efficacy.

Other names

Prostate stromal-epithelial crosstalkProstate cancer-associated fibroblast signalingParacrine signaling in prostate stromaStromal-epithelial interactions in the prostate

Inhibition of paracrine growth factors, blockade of stromal-derived chemokines, and disruption of stromal-epithelial crosstalk pathways such as TGF-beta, FGF, and Wnt signaling.