Endothelial-rich microenvironment supports growth and branching morphogenesis of prostate epithelial cells
Endothelial-rich microenvironment supports growth and branching morphogenesis of prostate epithelial cells
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DOI：
10.1002/pros.22634
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发表时间：
2013-06-01
期刊：
影响因子：
2.8
通讯作者：
Gudjonsson, Thorarinn
中科院分区：
文献类型：
--
作者：
Bergthorsson, Jon Thor;Magnusson, Magnus Karl;Gudjonsson, Thorarinn
背景技术上皮器官的发育取决于上皮和下面的间充质（包括脉管系统）之间的相互作用。本研究的目的是探讨3D培养中内皮细胞对前列腺上皮细胞系的形态发生作用，并建立前列腺分支形态发生的体外模型。方法将一组源自正常或恶性前列腺和原代前列腺上皮细胞的十一种细胞系培养在重建的基底膜（rBM）基质中，有或没有非增殖但代谢活跃的内皮细胞。通过相差显微镜评估形态发生，并通过免疫细胞/组织化学和共聚焦显微镜进一步表征。结果内皮细胞诱导大多数前列腺细胞系的克隆形成潜力以及分支和间质样集落的形成。该组中的一种正常来源的细胞系 (PZ-HPV-7) 通过形成类似于前列腺导管结构的大型且复杂的分支结构，在 rBM 培养物中显示出独特的特性。这种能力高度依赖于上皮接种密度和源自内皮细胞的可溶性因子。高接种密度抑制了 PZ-HPV-7 的分支，但在缺乏内皮的情况下，低密度下的存活率受到损害。结论我们已经开发出一种基于内皮细胞的克隆形成测定法来研究三维背景下的前列腺上皮形态发生。该测定将成为研究 3D 背景下前列腺上皮内皮相互作用的重要工具，并为研究前列腺形态发生和癌症进展的分子调控开辟了可能性。前列腺 73：884896，2013。(c) 2012 Wiley periodicals, Inc.
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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 epithelialendothelial interactions in 3D context and open up possibilities to study molecular regulation of prostate morphogenesis and cancer progression. Prostate 73: 884896, 2013. (c) 2012 Wiley Periodicals, Inc.