血管生成
MAPK/ERK通路
癌症研究
半乳糖凝集素-3
分泌物
激酶
蛋白激酶A
内皮干细胞
肿瘤进展
生物
细胞生物学
癌症
免疫学
内分泌学
生物化学
体外
遗传学
作者
Victor L. Thijssen,Batya Barkan,Hiromichi Shoji,Ingrid M. Ariës,Véronique Mathieu,Louise Deltour,Tilman M. Hackeng,Róbert Kiss,Yoel Kloog,Françoise Poirier,Arjan W. Griffioen
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2010-07-28
卷期号:70 (15): 6216-6224
被引量:211
标识
DOI:10.1158/0008-5472.can-09-4150
摘要
Tumor angiogenesis is a key event in cancer progression. Here, we report that tumors can stimulate tumor angiogenesis by secretion of galectin-1. Tumor growth and tumor angiogenesis of different tumor models are hampered in galectin-1-null (gal-1(-/-)) mice. However, tumor angiogenesis is less affected when tumor cells express and secrete high levels of galectin-1. Furthermore, tumor endothelial cells in gal-1(-/-) mice take up galectin-1 that is secreted by tumor cells. Uptake of galectin-1 by cultured endothelial cells specifically promotes H-Ras signaling to the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk) kinase (Mek)/Erk cascade and stimulates endothelial cell proliferation and migration. Moreover, the activation can be blocked by galectin-1 inhibition as evidenced by hampered membrane translocation of H-Ras.GTP and impaired Raf/Mek/Erk phosphorylation after treatment with the galectin-1-targeting angiogenesis inhibitor anginex. Altogether, these data identify galectin-1 as a proangiogenic factor. These findings have direct implications for current efforts on galectin-1-targeted cancer therapies.
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