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Molecular and Cellular Pathobiology

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 and Arjan W. Griffioen
Victor L. Thijssen
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Batya Barkan
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Hiroki Shoji
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Ingrid M. Aries
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Véronique Mathieu
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Louise Deltour
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Tilman M. Hackeng
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Robert Kiss
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Yoel Kloog
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Françoise Poirier
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Arjan W. Griffioen
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DOI: 10.1158/0008-5472.CAN-09-4150
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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. ©2010 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received November 11, 2009.
  • Revision received May 10, 2010.
  • Accepted May 27, 2010.
  • ©2010 American Association for Cancer Research.
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Published OnlineFirst July 20, 2010
doi: 10.1158/0008-5472.CAN-09-4150

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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 and Arjan W. Griffioen
Cancer Res July 20 2010 DOI: 10.1158/0008-5472.CAN-09-4150

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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 and Arjan W. Griffioen
Cancer Res July 20 2010 DOI: 10.1158/0008-5472.CAN-09-4150
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Cancer Research Online ISSN: 1538-7445
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