Pepper M S, Ferrara N, Orci L, Montesano R
Department of Morphology, University Medical Center, Geneva, Switzerland.
J Cell Sci. 1995 Jan;108 ( Pt 1):73-83. doi: 10.1242/jcs.108.1.73.
Using an in vitro model in which endothelial cells can be induced to invade a three-dimensional collagen gel to form capillary-like tubular structures, we demonstrate that leukemia inhibitory factor (LIF) inhibits angiogenesis in vitro. The inhibitory effect was observed on both bovine aortic endothelial (BAE) and bovine microvascular endothelial (BME) cell, and occurred irrespective of the angiogenic stimulus, which included basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), the synergistic effect of the two in combination, or the tumor promoter phorbol myristate acetate. LIF inhibited bFGF- and VEGF-induced proliferation in BAE and BME cells. In addition, LIF inhibited BAE but not BME cell migration in a conventional two-dimensional assay. Finally, LIF decreased the proteolytic activity of BAE and BME cells and increased their expression of plasminogen activator inhibitor-1. These results demonstrate that LIF inhibits angiogenesis in vitro, an effect that can be correlated with a LIF-mediated decrease in endothelial cell proliferation, migration and extracellular proteolysis.
利用一种体外模型，其中内皮细胞可被诱导侵入三维胶原凝胶以形成毛细血管样管状结构，我们证明白血病抑制因子（LIF）在体外抑制血管生成。在牛主动脉内皮（BAE）细胞和牛微血管内皮（BME）细胞上均观察到抑制作用，且该抑制作用与血管生成刺激无关，血管生成刺激包括碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、两者联合的协同作用或肿瘤启动子佛波酯肉豆蔻酸酯。LIF抑制BAE细胞和BME细胞中bFGF和VEGF诱导的增殖。此外，在传统的二维试验中，LIF抑制BAE细胞迁移，但不抑制BME细胞迁移。最后，LIF降低了BAE细胞和BME细胞的蛋白水解活性，并增加了它们纤溶酶原激活物抑制剂-1的表达。这些结果表明，LIF在体外抑制血管生成，这种作用可能与LIF介导的内皮细胞增殖、迁移和细胞外蛋白水解减少有关。
