Tumor Cells Secrete Galectin-1 to Enhance Endothelial Cell Activity

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

159 Citations (Web of Science)

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. Cancer Res; 70(15); 6216-24.
Original languageEnglish
Pages (from-to)6216-6224
JournalCancer Research
Volume70
Issue number15
DOIs
Publication statusPublished - 1 Aug 2010

Cite this