Disclosure statement: None of the authors has affiliations with an organization that may in any way gain or lose financially from the publication of this manuscript or have other competing interests to declare.
Endothelial-rich microenvironment supports growth and branching morphogenesis of prostate epithelial cells†
Article first published online: 31 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 73, Issue 8, pages 884–896, June 2013
How to Cite
Bergthorsson, J. T., Magnusson, M. K. and Gudjonsson, T. (2013), Endothelial-rich microenvironment supports growth and branching morphogenesis of prostate epithelial cells. Prostate, 73: 884–896. doi: 10.1002/pros.22634
- Issue published online: 25 APR 2013
- Article first published online: 31 DEC 2012
- Manuscript Accepted: 3 DEC 2012
- Manuscript Received: 6 SEP 2012
- Icelandic Centre for Research. Grant Number: 100444042
- Icelandic Cancer Society, University of Iceland Research Fund
- Bergthora Magnusdottir and Jakob J. Bjarnasson Memory Fund
- prostate morphogenesis;
- stem cells;
- endothelial cells;
- three-dimensional culture
Development of epithelial organs depends on interaction between the epithelium and the underlying mesenchyme including the vasculature. The aim of this study was to explore the morphogenic effect of endothelial cells on prostate epithelial cell lines in 3D culture and to establish an in vitro model for prostate branching morphogenesis.
A panel of eleven cell lines originating in normal or malignant prostate and primary prostate epithelial cells were cultured in reconstituted basement membrane (rBM) matrix with or without non-proliferating but metabolically active endothelial cells. Morphogenesis was evaluated by phase contrast microscopy and further characterized by immunocyto/histocemistry and confocal microscopy.
Endothelial cells induced clonogenic potential of most prostate cell lines and formation of branching and mesenchymal-like colonies. One of the normal-derived cell lines in the panel (PZ-HPV-7) displayed unique properties in rBM culture by forming large and complex branching structures resembling the ductal architecture of the prostate. This ability was highly dependent on epithelial seeding density and soluble factors derived from the endothelial cells. High seeding density suppressed branching of PZ-HPV-7 but survival was compromised at low density in the absence of endothelium.
We have generated an endothelial-based clonogenic assay to study prostate epithelial morphogenesis in three-dimensional context. This assay will be important tool to study prostate epithelial–endothelial interactions in 3D context and open up possibilities to study molecular regulation of prostate morphogenesis and cancer progression. Prostate 73: 884–896, 2013. © 2012 Wiley Periodicals, Inc.