Tumor cells secrete galectin-1 to enhance endothelial cell activity.
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.
Thijssen
Victor L
VL
Department of Radiotherapy, Angiogenesis Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
Barkan
Batya
B
Shoji
Hiroki
H
Aries
Ingrid M
IM
Mathieu
Véronique
V
Deltour
Louise
L
Hackeng
Tilman M
TM
Kiss
Robert
R
Kloog
Yoel
Y
Poirier
Françoise
F
Griffioen
Arjan W
AW
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D037483:Galectin 1 / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D018243:Teratocarcinoma / Q000098:blood supply* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D037483:Galectin 1; D011994:Recombinant Proteins; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins