title: Polarized fluid movement and not cell death, creates luminal spaces in adult prostate epithelium.
abstract: There are two predominant theories for lumen formation in tissue morphogenesis: cavitation driven by cell death, and membrane separation driven by epithelial polarity. To define the mechanism of lumen formation in prostate acini, we examined both theories in several cell lines grown in three-dimensional (3D) Matrigel culture. Lumen formation occurred early in culture and preceded the expression of cell death markers for apoptosis (active caspase 3) and autophagy (LC-3). Active caspase 3 was expressed by very few cells and inhibition of apoptosis did not suppress lumen formation. Despite LC-3 expression in all cells within a spheroid, this was not associated with cell death. However, expression of a prostate-secretory protein coincided with lumen formation and subsequent disruption of polarized fluid movement led to significant inhibition of lumen formation. This work indicates that lumen formation is driven by the polarized movement of fluids and proteins in 3D prostate epithelial models and not by cavitation.
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, Heslington, York YO10 5YW, UK.
authors.forename: J F
authors.initials: JF
authors.lastname: Pearson
authors.forename: S
authors.initials: S
authors.lastname: Hughes
authors.forename: K
authors.initials: K
authors.lastname: Chambers
authors.forename: S H
authors.initials: SH
authors.lastname: Lang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D016923:Cell Death / Q000502:physiology*; D016764:Cell Polarity; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000033:anatomy & histology / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D009024:Morphogenesis / Q000502:physiology; D010042:Ouabain / Q000378:metabolism; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D010042:Ouabain; D003094:Collagen