Galectin-3 stimulates cell proliferation

Galectin-3, a beta-galactoside-binding protein, has been shown to be involv ed in multiple biological processes through interaction with its complement ary glycoconjugates. Here we provide the first evidence of galectin-3 as a mitogen. Incubation of quiescent cultures of normal human lung fibroblast I MR-90 cells with recombinant galectin-3 (rgalectin-3) stimulated DNA synthe sis as well as cell proliferation in a dose-dependent manner. This mitogeni c activity was dependent on the lectin property of galectin-3, as it could be significantly inhibited by lactose, a disaccharide competitive for carbo hydrate-binding by galectin-3. Chemical cross-linking and affinity-purifica tion experiments identified binding of rgalectin-3 to cell surface glycopro teins, which were not recognized by antibodies directed against lysosome-as sociated membrane proteins (LAMPs), putative cellular ligands for galectin- 3. Moreover, pulse-chase analysis revealed no secretion of galectin-3 by IM R-90 cells. These results indicate that galectin-3 is a mitogen capable of stimulating fibroblast cell proliferation in a paracrine fashion through in teraction with cell surface glycoconjugates different from LAMPs and sugges t a possible involvement of galectin-3 in tissue remodeling. (C) 1998 Acade mic Press.