Keratoepithelin suppresses the progression of experimental human neuroblastomas
Keratoepithelin suppresses the progression of experimental human neuroblastomas
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DOI：
10.1158/0008-5472.can-05-3049
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发表时间：
2006-05-15
期刊：
影响因子：
11.2
通讯作者：
Schweigerer, Lothar
中科院分区：
文献类型：
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作者：
Becker, Juergen;Erdlenbruch, Bernhard;Schweigerer, Lothar
神经母细胞瘤是最常见的儿童颅外肿瘤。激活素A的高表达与良好的预后相关，但其作用机制尚不清楚。我们先前对激活素A介导的角膜上皮素上调的证明导致考虑角膜上皮素可以调节神经母细胞瘤生长和/或进展。我们在这里报告，增强人神经母细胞瘤细胞中的keratoepithelin表达抑制神经母细胞瘤细胞的凝聚力和粘附各种细胞外基质蛋白，它抑制神经母细胞瘤细胞的增殖和入侵在体外和体内。使用微阵列分析，我们确定了几个角膜上皮调节基因，可能有助于这些生物学变化。结合角膜上皮素在体内人神经母细胞瘤中表达的观察结果，我们的数据表明，角膜上皮素在神经母细胞瘤的发展和/或进展中可能发挥有益的作用。
Neuroblastoma is the most common extracranial childhood tumor. High expression of activin A is associated with a favorable prognosis, but the contributing mechanisms have remained unclear. Our previous demonstration of the activin A-mediated up-regulation of keratoepithelin led to the consideration that keratoepithelin could modulate neuroblastoma growth and/or progression. We report here that enhanced keratoepithelin expression in human neuroblastoma cells suppresses neuroblastoma cell cohesion and adhesion to various extracellular matrix proteins and that it inhibits neuroblastorna cell proliferation and invasion in vitro and in vivo. Using microarray analysis, we identified several keratoepithelin-regulated genes that may contribute to these biological changes. Together with the observation that keratoepithelin is expressed in human neuroblastomas in vivo, our data suggest that keratoepithelin could play a beneficial role in neuroblastoma development and/or progression.