Colon Cancer Mucin: A New Ligand for the ß-Galactoside-binding Protein Galectin-31

GuliTiiii-3. an endogenous ß-galactoside-binding lectin. is present on colon cancer cells and may play a role in metastasis. Galcctin-3 hinds poly-.V-acetyllactosamine structures on glycoproteins. but its natural li gands remain to be fully defined. Galectin-3 bound to purified native and desialylated colon cancer mucin in a concentration-dependent manner, which »ascompletely inhibited by 0.1 M lactose, the competitive inhibi tory sugar for this protein. Mucin purified from highly metastatic I,S-l ,iin6 human colon cancer cells bound galectin-3 to a 2-fold greater extent than mucin from low-metastatic parental cell line LS174Õ. Desialylation increased binding to mucin >4-fold. Mucin purified from IS-1! colon cancer cells is fully glycosylated and bound >4()-fold more galec tin-3 than mucin purified from clonal cell line I.S-t'. which produces mucin lacking peripheral carbohydrate structures. Endogenous galectin-3 «¡is detected by Western analysis in all cell lines, and its expression was related to mucin production and metastatic capacity. When serum from a patient with metastatic coloréela!cancer was chromatographed on Superose 6. >70'( of galectin-3 ligand was identified as circulating mucin. Colon cancer mucin is a newly identified ligand for galectin-3. and binding of galectin-3 to mm ins depends on peripheral carbohydrate structures. Binding of this endogenous lectin to mucins may influence cellular inter actions that play a role in colon cancer metastasis.