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.
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Abbreviations
- 3D:
-
three dimensional
- PSA:
-
prostate-specific antigen
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Acknowledgements
We thank Professor Norman Maitland for his generous support of the project and provision of Laboratory space. Many thanks to M Stower for providing prostate tissue samples. We also thank the members of the Yorkshire Cancer Research laboratory for their useful discussions and technical help. We are grateful to Dr. Anne Collins for her comments on the paper. This study was supported by the Wellcome Trust (GR076612MA), BBSRC (BB/E021409/1) and Yorkshire Cancer Research.
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Pearson, J., Hughes, S., Chambers, K. et al. Polarized fluid movement and not cell death, creates luminal spaces in adult prostate epithelium. Cell Death Differ 16, 475–482 (2009). https://doi.org/10.1038/cdd.2008.181
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DOI: https://doi.org/10.1038/cdd.2008.181
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