TY - JOUR
T1 - A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer
AU - Bresalier, Robert S.
AU - Byrd, James C.
AU - Tessler, David
AU - Lebel, Joseph
AU - Koomen, John
AU - Hawke, David
AU - Half, Elizabeth
AU - Liu, Kai Feng
AU - Mazurek, Nachman
N1 - Funding Information:
Supported by National Cancer Institute grants R01CA69480 and U01CA86400.
PY - 2004/9
Y1 - 2004/9
N2 - Background & Aims: Galectin-3 is a β-galactoside-binding protein implicated in tumor progression and metastasis of colorectal cancers. To determine whether circulating galectin-3 ligands are related to the presence of colon cancer, we sought to identify and quantify ligands in serum that bind to galectin-3. Methods: Sera from patients with colon cancer, adenomas, and normal individuals were desialylated, reduced, and separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and blots probed with biotinylated galectin-3. Results: In colon cancer sera, the major galectin-3 ligand was a 40-kilodalton band distinct from mucin, carcinoembryonic antigen, and Mac-2 binding protein. Serum 40-kilodalton ligand was 10- to 30-fold higher in patients with colon cancer than in healthy subjects. Ligand was purified by gel filtration, affinity precipitation on galectin-3/agarose, and SDS-PAGE. When tryptic peptides were analyzed by matrix-assisted laser-desorption ionization mass spectrometry and protein database searching, the 40-kilodalton ligand was identified as haptoglobin β subunit. In confirmation of this finding, depletion of haptoglobin by immunoprecipitation also eliminated the 40-kilodalton ligand. Colon cancer sera had only a modest increase in total haptoglobin as compared with healthy subjects, suggesting that the structure rather than the amount of haptoglobin is altered in patients with colon cancer. Immunohistochemical staining confirmed the absence of haptoglobin in normal colon and the ectopic expression of haptoglobin in colon cancers and adenomatous polyps. Conclusions: A major circulating ligand for galectin-3, which is elevated in the sera of patients with colon cancer, is a cancer-associated glycoform of haptoglobin.
AB - Background & Aims: Galectin-3 is a β-galactoside-binding protein implicated in tumor progression and metastasis of colorectal cancers. To determine whether circulating galectin-3 ligands are related to the presence of colon cancer, we sought to identify and quantify ligands in serum that bind to galectin-3. Methods: Sera from patients with colon cancer, adenomas, and normal individuals were desialylated, reduced, and separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and blots probed with biotinylated galectin-3. Results: In colon cancer sera, the major galectin-3 ligand was a 40-kilodalton band distinct from mucin, carcinoembryonic antigen, and Mac-2 binding protein. Serum 40-kilodalton ligand was 10- to 30-fold higher in patients with colon cancer than in healthy subjects. Ligand was purified by gel filtration, affinity precipitation on galectin-3/agarose, and SDS-PAGE. When tryptic peptides were analyzed by matrix-assisted laser-desorption ionization mass spectrometry and protein database searching, the 40-kilodalton ligand was identified as haptoglobin β subunit. In confirmation of this finding, depletion of haptoglobin by immunoprecipitation also eliminated the 40-kilodalton ligand. Colon cancer sera had only a modest increase in total haptoglobin as compared with healthy subjects, suggesting that the structure rather than the amount of haptoglobin is altered in patients with colon cancer. Immunohistochemical staining confirmed the absence of haptoglobin in normal colon and the ectopic expression of haptoglobin in colon cancers and adenomatous polyps. Conclusions: A major circulating ligand for galectin-3, which is elevated in the sera of patients with colon cancer, is a cancer-associated glycoform of haptoglobin.
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U2 - 10.1053/j.gastro.2004.06.016
DO - 10.1053/j.gastro.2004.06.016
M3 - Article
C2 - 15362030
AN - SCOPUS:4444360281
SN - 0016-5085
VL - 127
SP - 741
EP - 748
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -