Ueda Eric, Ozerdem Ugur, Chen Yen-Hao, Yao Min, Huang Kuang Tzu, Sun Huiqin, Martins-Green Manuela, Bartolini Paolo, Walker Ameae M
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA.
Endocr Relat Cancer. 2006 Mar;13(1):95-111. doi: 10.1677/erc.1.01076.
S179D prolactin (PRL) is an experimentally useful mimic of naturally phosphorylated human prolactin. S179D PRL, but not unmodified PRL, was found to be anti-angiogenic in both the chorioallantoic membrane and corneal assays. Further investigation using human endothelial in vitro models showed reduced cell number, reduced tubule formation in Matrigel, and reduced migration and invasion, as a function of treatment with S179D PRL. Analysis of growth factors in human endothelial cells in response to S179D PRL showed: a decreased expression or release of endogenous PRL, heme-oxygenase-1, basic fibroblast growth factor (bFGF), angiogenin, epidermal growth factor and vascular endothelial growth factor; and an increased expression of inhibitors of matrix metalloproteases. S179D PRL also blocked signaling from bFGF in these cells. We conclude that this molecular mimic of a pituitary hormone is a potent anti-angiogenic protein, partly as a result of its ability to reduce utilization of several well-established endothelial autocrine growth loops, partly by its ability to block signaling from bFGF and partly because of its ability to decrease endothelial migration. These findings suggest that circulating levels of phosphorylated PRL may influence the progression of cancer and, furthermore, that S179D PRL may be a useful anti-angiogenic therapeutic.
S179D催乳素（PRL）是一种在实验中很有用的天然磷酸化人催乳素模拟物。研究发现，S179D PRL而非未修饰的PRL在绒毛尿囊膜和角膜试验中均具有抗血管生成作用。使用人内皮细胞体外模型进行的进一步研究表明，作为S179D PRL处理的一项功能，细胞数量减少、基质胶中小管形成减少以及迁移和侵袭减少。对人内皮细胞中响应S179D PRL的生长因子分析显示：内源性PRL、血红素加氧酶-1、碱性成纤维细胞生长因子（bFGF）、血管生成素、表皮生长因子和血管内皮生长因子的表达或释放减少；基质金属蛋白酶抑制剂的表达增加。S179D PRL还阻断了这些细胞中bFGF的信号传导。我们得出结论，这种垂体激素的分子模拟物是一种有效的抗血管生成蛋白，部分原因是其能够减少几种成熟的内皮自分泌生长环的利用，部分原因是其能够阻断bFGF的信号传导，部分原因是其能够减少内皮迁移。这些发现表明，磷酸化PRL的循环水平可能影响癌症进展，此外，S179D PRL可能是一种有用的抗血管生成治疗药物。
