Acute phase glycoproteins: bystanders or participants in carcinogenesis?

Acute phase proteins (APPs) are a group of serum proteins that undergo dramatic changes in concentration during times of inflammation. Many APPs are heavily glycosylated, and their sugar content and complexity change in the presence of cancer-induced chronic inflammation. These changes in glycosylation are currently being exploited in the search for novel biomarkers of cancer. Like other posttranslational modifications, such as phosphorylation, changes in glycosylation can profoundly alter the function of a protein. We hypothesize that besides being a rich source of potential biomarkers APPs may also play an active role in tumorigenesis. The glycan content of the APPs haptoglobin and kininogen, for example, is altered in many types of cancer. These APPs can interact with a number of receptors on macrophages in the tumor microenvironment, potentially modulating macrophage activity and thereby contributing to tumor cell survival, growth, and metastasis.