Expression of human intestinal mucin is modulated by the beta-galactoside binding protein galectin-3 in colon cancer.
OBJECTIVE
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.
Gastrointestinal Cancer Research Laboratory, Henry Ford Health Sciences Center, Detroit, Michigan, USA.
Steven P
SP
Dudas
Christopher K
CK
Yunker
Lawrence R
LR
Sternberg
James C
JC
Byrd
Robert S
RS
Bresalier
D000818:Animals; D000943:Antigens, Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002999:Clone Cells / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D005697:Galactosides / Q000378:metabolism*; D037502:Galectin 3; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D055262:Mucin-2; D009077:Mucins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D005697:Galactosides; D037502:Galectin 3; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; C007816:beta-galactoside