Tumor cells secrete galectin-1 to enhance endothelial cell activity

Victor L. Thijssen, Batya Barkan, Hiroki Shoji, Ingrid M. Aries, Véronique Mathieu, Louise Deltour, Tilman M. Hackeng, Robert Kiss, Yoel Kloog, Françoise Poirier, Arjan W. Griffioen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)6216-6224
Number of pages9
JournalCancer Research
Volume70
Issue number15
DOIs
StatePublished - 1 Aug 2010

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