Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells.
Galectin-3 is an endogenous beta-galactoside-binding protein with specificity for type I and II ABH blood group epitopes and poly-N-acetyllactosamine glycan-containing cell surface glycoproteins and is the major nonintegrin cellular laminin-binding protein. Galectin-3 is expressed at an elevated level in a wide range of neoplasms, and expression was shown to be associated in some tumor cell systems with metastases. Here we determined the functional consequence of blocking galectin-3 expression in highly malignant human breast carcinoma MDA-MB-435 cells. Inhibition of galectin-3 expression led to reversion of the transformed phenotype as determined by altered morphology, loss of serum-independent growth, acquisition of growth inhibition properties by cell contact, and abrogation of anchorage-independent growth. The blockage of galectin-3 expression led to a significant suppression of tumor growth in nude mice. These results provide direct evidence that galectin-3 expression is necessary for the maintenance of the transformed and tumorigenic phenotype of MDA-MB-435 breast carcinoma cells.
Honjo
Y
Y
Karmanos Cancer Institute and Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.
Nangia-Makker
P
P
Inohara
H
H
Raz
A
A
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division; D015536:Down-Regulation; D037502:Galectin 3; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D037502:Galectin 3; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins