Novel Technology May Allow the Use of Autoantibodies as Cancer Biomarkers
The Bottom Line
A new technology that enables the detection of antibodies in the blood that target abnormal glycoproteins produced by cancer cells may make it possible to use these antibodies as biomarkers for the early detection of cancer.
The Whole Story
Cancer cells can express molecules on their surface that are not usually found on the surface of normal cells. Sometimes, the immune system will recognize these molecules as being “foreign” and produce antibodies against them as a defense mechanism. Because the targeted molecules are on a person’s own cells, the antibodies are called “autoantibodies.” Autoantibodies alone are rarely sufficient to kill cancer cells, but they may prove useful as biomarkers to detect cancer early.
In this study, the researchers identified and analyzed autoantibodies directed against abnormal forms of the protein MUC-1, which is a member of a family of proteins called mucins. Mucins are found in the plasma membrane (outer membrane) of epithelial cells and, during their production, are modified by the addition of carbohydrate (sugar) molecules in a process known as glycosylation. Previous research had shown that MUC-1 is produced in larger amounts by many types of cancer cells and that it is abnormally glycosylated by those cells.
To detect autoantibodies against aberrantly glycosylated forms of MUC-1, the researchers had to develop a new technology in which they used enzymes to attach sugar molecules to MUC-1 peptides (fragments) in the laboratory. This process yielded a diverse “library” of molecules called glycopeptides that included molecules containing the abnormal carbohydrates previously found on cancer cells. Next, the researchers attached the members of this glycopeptide library to a special type of slide to create “microarrays,” which they subsequently used to screen the blood (serum) of newly diagnosed patients with breast, ovarian, or prostate cancer, as well as serum from normal control subjects, for the presence of antibodies against abnormal forms of MUC-1.
The scientists found that the serum from cancer patients contained immunoglobulin G (IgG) antibodies that reacted with members of the glycopeptide library. From patient to patient, these antibodies were present in differing amounts and specificities. In contrast, IgG antibodies in the serum of healthy control subjects did not react with members of the glycopeptide library.
According to the researchers, this study should be viewed as a proof-of-concept study, and much more work is required before a clinically useful assay, or assays, based on their findings can be developed. Moreover, although many common cancer types overproduce MUC-1, many do not. Therefore, extending this approach to other cancer types will require the identification of additional glycoproteins that are aberrantly expressed in cancer. Nevertheless, it is hoped that refinements of this technology will lead to disease-specific assays that can be used to diagnose many cancers earlier, when they may be most treatable.
The study was an international collaboration funded in part by the National Cancer Institute (NCI) through the trans-NIH Alliance of Glycobiologists for Detection of Cancer and Cancer Risk. The alliance is a consortium of NCI-supported laboratories that are working to reveal the cancer-related dynamics of complex carbohydrates and develop biomarkers for early cancer detection and risk assessment.
More summaries of selected scientific advances from NCI-supported research are available at http://www.cancer.gov/aboutnci/servingpeople/advances.