Wickström Sara A, Alitalo Kari, Keski-Oja Jorma
Department of Pathology, Haartman Institute, University of Helsinki, Biomedicum Helsinki and Helsinki University Hospital, FIN-00014 Helsinki, Finland.
J Biol Chem. 2004 May 7;279(19):20178-85. doi: 10.1074/jbc.M312921200. Epub 2004 Feb 18.
Endostatin, the C-terminal fragment of collagen XVIII, is a potent inhibitor of angiogenesis and endothelial cell migration. To define its critical cell interaction domains we used endostatin-derived synthetic peptides containing surface-exposed sequences. We observed that, when immobilized, an arginine-rich peptide of 11 amino acids from its N terminus efficiently promoted endothelial cell adhesion through beta(1) integrin- and heparin-dependent mechanisms. In addition, the peptide induced the formation of membrane ruffles and focal contacts. In the soluble form, the peptide inhibited basic fibroblast growth factor-induced directional migration and tubular morphogenesis of microvascular endothelial cells. Accordingly, the peptide induced the loss of focal adhesions and actin stress fibers in these cells. Substitution of the arginine residues with alanines resulted in the loss of these properties. In the current study we describe a putative integrin-binding sequence with anti-migratory activity within endostatin.
内皮抑素是胶原蛋白 XVIII 的 C 末端片段，是一种有效的血管生成和内皮细胞迁移抑制剂。为了确定其关键的细胞相互作用结构域，我们使用了含有表面暴露序列的内皮抑素衍生合成肽。我们观察到，固定化时，来自其 N 末端的一个 11 个氨基酸的富含精氨酸的肽通过 β(1)整合素和肝素依赖性机制有效地促进内皮细胞粘附。此外，该肽诱导膜皱襞和粘着斑的形成。以可溶形式存在时，该肽抑制碱性成纤维细胞生长因子诱导的微血管内皮细胞的定向迁移和管状形态发生。因此，该肽导致这些细胞中粘着斑和肌动蛋白应力纤维的丧失。用丙氨酸取代精氨酸残基导致这些特性丧失。在本研究中，我们描述了内皮抑素内一个具有抗迁移活性的假定整合素结合序列。
