First Author | Thijssen VL | Year | 2010 |
Journal | Cancer Res | Volume | 70 |
Issue | 15 | Pages | 6216-24 |
PubMed ID | 20647324 | Mgi Jnum | J:162228 |
Mgi Id | MGI:4818493 | Doi | 10.1158/0008-5472.CAN-09-4150 |
Citation | Thijssen VL, et al. (2010) Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity. Cancer Res 70(15):6216-6224 |
abstractText | 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. Cancer Res; 70(15); 6216-24. (c)2010 AACR. |