Medical University of Vienna, Centre for Pathobiochemistry and Genetic, Inst. Med. Chem., Waehringerstr. 10/13, A-1090 Vienna, Austria.
Biochimie. 2010 Jul;92(7):880-4. doi: 10.1016/j.biochi.2010.03.013. Epub 2010 Mar 25.
Lactoferrin (Lf) is a multifunctional glycoprotein. Due to its anti-inflammatory and anti-cancer properties and the resulting therapeutical potential, lactoferrin is at present focus of a variety of research areas. The regulation of cell growth represents one of the prominent performances of lactoferrin. In this study we found lactoferrin to inhibit proliferation of the human epithelial cancer cell line HeLa. The extent of this growth inhibition was comparable to the one induced by the transforming-growth-factor-beta-1 (TGFbeta1). In contrast to other cell lines where lactoferrin stimulates growth, lactoferrin failed to activate the MAP kinases ERK1/2 or p38 in HeLa cells. However, by immunocytochemistry and cell fractionation experiments, we found that lactoferrin is capable of activating the TGFbeta/Smad-2 pathway. The nuclear accumulation of Smad-2 induced by Lf was comparable in magnitude to the one induced by TGFbeta1. We therefore conclude that the canonical TGFbeta1 pathway is a feasible route for lactoferrin to transduce its antiproliferative effect in HeLa cells, when MAPkinase activation is absent.
乳铁蛋白（Lf）是一种多功能糖蛋白。由于其具有抗炎和抗癌特性以及由此产生的治疗潜力，乳铁蛋白目前是各种研究领域的焦点。细胞生长的调节是乳铁蛋白的突出表现之一。在这项研究中，我们发现乳铁蛋白抑制人上皮癌细胞系 HeLa 的增殖。这种生长抑制的程度与转化生长因子-β-1（TGFβ1）诱导的程度相当。与其他促进细胞生长的细胞系不同，乳铁蛋白不能激活 HeLa 细胞中的 MAP 激酶 ERK1/2 或 p38。然而，通过免疫细胞化学和细胞分级实验，我们发现乳铁蛋白能够激活 TGFβ/Smad-2 途径。Lf 诱导的 Smad-2 核积累的幅度与 TGFβ1 诱导的幅度相当。因此，当 MAP 激酶激活不存在时，我们得出结论，经典的 TGFβ1 途径是乳铁蛋白在 HeLa 细胞中传递其抗增殖作用的可行途径。
