Galectin-3 induces endothelial cell morphogenesis and angiogenesis.
Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis. However, conflicting results on their function in the regulation of cell proliferation and differentiation during angiogenesis have been reported. We have examined the role of galectin-3 in the regulation of human umbilical vein endothelial cell proliferation, differentiation, migration, and neovascularization. Galectin-3, a carbohydrate-binding protein, with specificity for type 1 and 11 ABH blood group epitopes and polylactosamine glycan containing cell surface glycoproteins, is the major nonintegrin cellular laminin-binding protein. Because galectin-3 expression was shown to be associated in some tumor systems with metastasis, we questioned whether it induces endothelial cell morphogenesis. Here we show that galectin-3 affects chemotaxis and morphology and stimulates capillary tube formation of HUV-EC-C in vitro and angiogenesis in vivo. Endothelial cell morphogenesis is a carbohydrate-dependent process, as it is neutralized by specific sugars and antibodies. These findings demonstrate that endothelial cell surface carbohydrate recognition event(s) can induce a signaling cascade leading to the differentiation and angiogenesis of endothelial cells.
Nangia-Makker
P
P
Department of Tumor Progression, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Honjo
Y
Y
Sarvis
R
R
Akahani
S
S
Hogan
V
V
Pienta
K J
KJ
Raz
A
A
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism / Q000494:pharmacology*; D002196:Capillaries / Q000166:cytology; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D037502:Galectin 3; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012878:Skin Neoplasms / Q000098:blood supply* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D037502:Galectin 3; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins