Galectin-3 stimulates cell proliferation.
Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in multiple biological processes through interaction with its complementary glycoconjugates. Here we provide the first evidence of galectin-3 as a mitogen. Incubation of quiescent cultures of normal human lung fibroblast IMR-90 cells with recombinant galectin-3 (rgalectin-3) stimulated DNA synthesis as well as cell proliferation in a dose-dependent manner. This mitogenic activity was dependent on the lectin property of galectin-3, as it could be significantly inhibited by lactose, a disaccharide competitive for carbohydrate-binding by galectin-3. Chemical cross-linking and affinity-purification experiments identified binding of rgalectin-3 to cell surface glycoproteins, which were not recognized by antibodies directed against lysosome-associated membrane proteins (LAMPs), putative cellular ligands for galectin-3. Moreover, pulse-chase analysis revealed no secretion of galectin-3 by IMR-90 cells. These results indicate that galectin-3 is a mitogen capable of stimulating fibroblast cell proliferation in a paracrine fashion through interaction with cell surface glycoconjugates different from LAMPs and suggest a possible involvement of galectin-3 in tissue remodeling.
Inohara
H
H
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, 48201, USA. hide@ent.med.osaka-u.ac.jp
Akahani
S
S
Raz
A
A
D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002846:Chromatography, Affinity; D003432:Cross-Linking Reagents; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D037502:Galectin 3; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000494:pharmacology; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008970:Molecular Weight; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D037502:Galectin 3; D006001:Glycoconjugates; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D004247:DNA; D007785:Lactose