A haptoglobin-like protein that may be secreted by colon cancer cells shows promise as a serum marker for the disease, according to a new report.
The potential marker, found at 10 to 30 times higher levels in the serum of colon cancer patients compared to healthy controls, is a glycoform of haptoglobin. Such post-transcriptional, altered forms of normal proteins are a “growing theme in terms of tumor related markers,” as is glycosylation, lead investigator Dr. Robert S. Bresalier of the M.D. Anderson Cancer Center, Houston, told Reuters Health.Dr. Bresalier and colleagues sought to identify ligands for galectin-3, a beta-galactoside-binding protein believed to play a role in the cellular adhesion and growth that has been linked to the progression and spread of colorectal cancers. Their ligand blot analyses identified a band of 40 kilodaltons as the major galectin-3 ligand in the sera of colon cancer patients. The researchers first tested for the ligand in individuals from known groups, and found it was elevated in colon cancer patients. Paired serum samples taken from four colon cancer patients before and six weeks after resection found levels of the protein had dropped. Their validation study, of blinded samples from 49 patients supplied by the Early Detection Research Network, found the protein was elevated in colon cancer patients compared to individuals with polyps, inflammatory bowel disease, and healthy controls. Adenoma patients showed slightly higher levels of the protein than controls, as did IBD patients.Only a small increase in total haptoglobin was seen in the colon cancer patients, suggesting that the increase in the 40-kilodalton ligand was likely due to “a cancer-associated alteration in the carbohydrates on haptoglobin that are recognized by galectin-3,” the researchers note. Studies of colon cancer tissue provided evidence that colon cancer cells produced the altered form of the protein.”Our working hypothesis is that the basis for the colon cancer-associated presence of the 40-kilodalton galectin-3 ligand in serum is a combination of tumor-specific ectopic expression of the haptoglobin protein together with a colon-specific glycoprotein biosynthetic pattern,” the researchers conclude.(Source: Gastroenterology 2004;127:741-748: Reuters Health: Anne Harding: Oncolink: October 2004.)