Background: Prostaglandin E-2 (PGE(2)) is a proinflammatory mediator and activates the canonical Wnt-beta-catenin signaling pathway in hematopoietic stem cells. The SZ95 cell line was established from human sebaceous gland cells and is studied as a model system for these cells. Given that 2D culture of SZ95 cells does not recapitulate the organization of sebaceous glands in situ, we developed a 3D culture system for these cells and examined the effects of PGE(2) on cell morphology and function. Results: SZ95 cells maintained in 3D culture formed organoids that mimicked the organization of sebaceous glands in situ, including the establishment of a basement membrane. Organoids exposed to PGE(2) were larger and adopted a more complex organization compared with control organoids. PGE(2) activated the canonical Wnt signaling pathway as well as increased cell viability and proliferation, mitochondrial metabolism, and lipid synthesis in the organoids. Conclusions: Culture of SZ95 cells in 3D culture system recapitulates the structure and susceptibility to PGE(2) of sebaceous glands in situ and should prove useful for studies of the response of these glands to inflammation and other environmental stressors. Our results also implicate PGE(2)-induced activation of canonical Wnt signalingpathway in regulation of the morphology,proliferation, and function of "semi-vivo" sebaceous glands. (C) 2013 Elsevier Inc. All rights reserved.