Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland

Several studies reported the concerted and mutual communication between the prostate epithelium and stroma, which determines the final organ architecture and function, but gets awry in cancer. Deciphering the mechanisms involved in this communication is crucial to find new therapeutic strategies. HS sequesters a number of secreted growth factors and cytokines, controlling their bioavailability to the target cells, suggesting that HS is an important regulator of the extracellular matrix (ECM) and a key player in the cell‐cell and cell‐microenvironment communication during prostate morphogenesis and physiology. We propose that by controlling HS biosynthesis and sulfation pattern, as well as the cleavage of the HS chain and/or the shedding of proteoglycans, epithelial and stromal cells are able to precisely tune the availability of signaling molecules and modulate ligand‐receptor interaction and intracellular signal transduction. Key Findings Embryonic and early postnatal prostate development is summarized Heparan sulfate ability to concentrate signaling molecules is put in the context of prostate development A model is proposed to include the participation of both epithelial and stromal cells in the synthesis and remodeling of the extracellular matrix and, hence, the content and distribution of heparan sulfate