Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling.
Bladder cancer cell in co-culture induces human stem cell differentiation to urothelial cells through paracrine FGF10 signaling.
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DOI：
10.1007/s11626-013-9662-9
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发表时间：
2013-12
影响因子：
2.1
通讯作者：
Koh, Chester J.
中科院分区：
文献类型：
--
作者：
Chung, Seyung S.;Koh, Chester J.
关键词：
FGF 10是胚胎表皮形态发生所必需的，包括脑发育、肺形态发生和肢芽形成的起始。在本研究中，我们研究了FGF 10作为干细胞向尿路上皮细胞分化的诱导因子的作用。为此，采用人多能干细胞体外系统。将人羊水干细胞与永生化膀胱癌细胞系共培养，诱导其定向分化为尿路上皮细胞。尿路上皮标志物，尿斑蛋白II，III和细胞角蛋白8，通过RT-PCR，免疫细胞化学和蛋白质印迹分析进行监测。共培养的干细胞开始表达尿斑蛋白II、III和细胞角蛋白8。从膀胱癌细胞中靶向敲除FGF 10基因可消除定向分化。此外，当用mek抑制剂阻断FGF 10下游信号传导时，共培养系统失去诱导尿路上皮分化的能力。外源性添加重组FGF 10蛋白促进干细胞分化为尿路上皮细胞系。总之，这份报告表明，旁分泌FGF 10信号刺激人类干细胞分化为尿路上皮细胞。目前的研究提供了深入了解FGF 10作为膀胱再生的主要生长因子的潜在作用及其在膀胱移植中的治疗应用。
FGF10 is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation. In this study, we investigated the role of FGF10 as a lead induction factor for stem cell differentiation toward urothelial cell. To this end, human multi-potent stem cell in vitro system was employed. Human amniotic fluid stem cells were co-cultured with immortalized bladder cancer lines to induce directed differentiation into urothelial cells. Urothelial markers, uroplakin II, III and cytokeratin 8, were monitored by RT-PCR, immunocytochemistry and western blot analysis. Co-cultured stem cells began to express uroplakin II, III and cytokeratin 8. Targeted FGF10 gene knock down from bladder cancer cells abolished the directed differentiation. In addition, when FGF10 downstream signaling was blocked with the mek inhibitor, the co-culture system lost the capacity to induce urothelial differentiation. Exogenous addition of recombinant FGF10 protein promoted stem cell differentiation into urothelium cell lineage. Together, this report suggests that paracrine FGF10 signaling stimulates the differentiation of human stem cell into urothelial cells. Current study provides insight into the potential role of FGF10 as a lead growth factor for bladder regeneration and its therapeutic application for bladder transplantation.
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