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Expression of human intestinal mucin is modulated by the beta-galactoside binding protein galectin-3 in colon cancer.
Authors: Dudas SP, Yunker CK, Sternberg LR, Byrd JC, Bresalier RS.
Source: Gastroenterology 2002 Sep;123(3):817-26
Gastrointestinal Cancer Research Laboratory, Henry Ford Health Sciences Center, Detroit, Michigan; and The Department of Gastrointestinal Medicine and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Background & Aims: Alterations in the production of the beta-galactoside binding protein galectin-3 and of MUC2 intestinal mucin have been independently correlated with the malignant behavior of human colon cancer cells. MUC2 mucin is a major ligand for galectin-3, and colon cancer cells that differ quantitatively in MUC2 expression may also vary in expression of galectin-3. The current study was designed to investigate the relationship between galectin-3 production and MUC2 mucin synthesis by human colon cancer cells. METHODS: The effect of galectin-3 on MUC2 mucin production was assessed by stable transfection of sense and antisense galectin-3 expression constructs under the control of constitutive or tetracycline-inducible promoters into human colon cancer cells. Galectin-3 and MUC2 expression were determined by fluorescence-activated cell sorter (cell surface galectin-3), Western and Northern analysis (galectin-3, MUC2), and gel filtration of secreted high-weight glycoprotein (MUC2). In vitro results were confirmed in vivo by analysis of cecal xenografts in athymic mice. RESULTS: Colon cancer cells with high levels of galectin-3 also had high levels of MUC2 mucin, whereas those with low galectin-3 levels had low MUC2 levels. Alterations in galectin-3 levels by expression of sense or antisense galectin-3 constructs resulted in parallel alterations of MUC2 protein and RNA. Induction of antisense to galectin-3 in vivo was associated with decreases in both galectin-3 and MUC2 protein in cecal xenografts. CONCLUSIONS: The beta-galactoside binding protein galectin-3 modulates the expression of its major ligand MUC2 mucin in human colon cancer cells. This may have important implications for understanding the role of galectin-3 in colon cancer metastasis.