Monica Montano1,2,3, Kenneth H Dinnon4, Logan Jacobs1, William Xiang1, Renato V Iozzo5, Wade Bushman1,3. 1. University of Wisconsin Madison, Department of Urology, Madison, Wisconsin. 2. University of Wisconsin Madison, Cellular and Molecular Pathology, Madison, Wisconsin. 3. University of Wisconsin Madison, Carbone Cancer Center, Clinical Sciences Center, Madison, Wisconsin. 4. University of North Carolina, Department of Microbiology and Immunology, Chapel Hill, North Carolina. 5. Sidney Kimmel Medical College at Thomas Jefferson University, Department of Pathology, Anatomy, and Cell Biology, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: Prostate ductal branching morphogenesis involves a complex spatiotemporal regulation of cellular proliferation and remodeling of the extracellular matrix (ECM) around the developing ducts. Decorin (Dcn) is a small leucine-rich proteoglycan known to sequester several growth factors and to act as a tumor suppressor in prostate cancer. RESULTS: Dcn expression in the developing prostate paralleled branching morphogenesis and was dynamically regulated by androgen and Hedgehog (Hh) signaling. DCN colocalized with collagen in the periductal stroma and acellular interstitium. Exogenous DCN decreased epithelial proliferation in ex vivo organ cultures of developing prostate, whereas genetic ablation of Dcn resulted in increased epithelial proliferation in the developing prostate. CONCLUSIONS: Dcn expression and localization in the developing prostate is consistent with a primary role in organizing collagen around the developing ducts. Regulation of Dcn expression appears to be complex, involving both androgen and Hh signaling. The growth inhibitory effect of Dcn suggests a unique linkage between a structural proteoglycan and epithelial growth regulation. This may serve to coordinate two elements of the morphogenetic process: ductal growth and organization of the collagen matrix around the nascent duct. Developmental Dynamics 247:679-685, 2018.
BACKGROUND: Prostate ductal branching morphogenesis involves a complex spatiotemporal regulation of cellular proliferation and remodeling of the extracellular matrix (ECM) around the developing ducts. Decorin (Dcn) is a small leucine-rich proteoglycan known to sequester several growth factors and to act as a tumor suppressor in prostate cancer. RESULTS:Dcn expression in the developing prostate paralleled branching morphogenesis and was dynamically regulated by androgen and Hedgehog (Hh) signaling. DCN colocalized with collagen in the periductal stroma and acellular interstitium. Exogenous DCN decreased epithelial proliferation in ex vivo organ cultures of developing prostate, whereas genetic ablation of Dcn resulted in increased epithelial proliferation in the developing prostate. CONCLUSIONS:Dcn expression and localization in the developing prostate is consistent with a primary role in organizing collagen around the developing ducts. Regulation of Dcn expression appears to be complex, involving both androgen and Hh signaling. The growth inhibitory effect of Dcn suggests a unique linkage between a structural proteoglycan and epithelial growth regulation. This may serve to coordinate two elements of the morphogenetic process: ductal growth and organization of the collagen matrix around the nascent duct. Developmental Dynamics 247:679-685, 2018.