Thijssen Victor L J L, Postel Ruben, Brandwijk Ricardo J M G E, Dings Ruud P M, Nesmelova Irina, Satijn Sietske, Verhofstad Nicole, Nakabeppu Yusaku, Baum Linda G, Bakkers Jeroen, Mayo Kevin H, Poirier Françoise, Griffioen Arjan W
Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Pathology, University Maastricht, 6202A2 Maastricht, The Netherlands.
Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15975-80. doi: 10.1073/pnas.0603883103. Epub 2006 Oct 16.
We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of different human tumors. Expression knockdown in cultured endothelial cells inhibits cell proliferation and migration. The importance of gal-1 in angiogenesis is illustrated in the zebrafish model, where expression knockdown results in impaired vascular guidance and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is demonstrated in gal-1-null mice, in which tumor growth is markedly impaired because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1-null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal-1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.
我们描述了半乳糖凝集素-1（gal-1）是血管生成抑制剂血管抑素（anginex）的受体，并且该蛋白对肿瘤血管生成至关重要。gal-1在不同人类肿瘤的内皮细胞中过度表达。在培养的内皮细胞中敲低其表达可抑制细胞增殖和迁移。斑马鱼模型说明了gal-1在血管生成中的重要性，敲低其表达会导致血管导向受损和功能失调血管的生长。gal-1在肿瘤血管生成中的作用在gal-1基因缺失小鼠中得到证明，在这些小鼠中，由于肿瘤血管生成不足，肿瘤生长明显受损。此外，gal-1基因缺失小鼠中的肿瘤生长不再对血管抑素的抗血管生成治疗产生反应。因此，gal-1调节肿瘤血管生成，是血管抑制性癌症治疗的一个靶点。
