GLYCOSYLATION OF ALPHA-1-PROTEINASE INHIBITOR AND HAPTOGLOBIN IN OVARIAN-CANCER - EVIDENCE FOR 2 DIFFERENT MECHANISMS

The change in glycosylation of the two acute-phase proteins, alpha-1-p roteinase inhibitor (API) and haptoglobin (Hp), in progressive ovarian cancer is different. This has been shown by monosaccharide analysis a nd lectin-binding studies of proteins purified from serum. In the glyc an chains of API, there is decreased branching (more biantennary chain s), less branches ending in alpha 2-3 sialic acid, more branches endin g in alpha 2-6 sialic acid and more fucose, probably linked alpha 1-6 to the core region. On the other hand, Hp shows increased branching (m ore triantennary chains), more branches ending in alpha 2-3 sialic aci d, less branches ending in alpha 2-6 sialic acid, and more fucose, pro bably in the alpha 1-3 linkage at the end of the chains. This is surpr ising because API and Hp are thought to be glycosylated by a common pa thway in the liver. We have also shown that the fucose-specific lectin , lotus tetragonolobus, extracts abnormal forms of bath Hp and API in ovarian cancer, but the expression of this Hp is related to tumour bur den and the expression of this API is related to lack of response to t herapy. It is suggested that this difference in the behaviour of API a nd Hp in ovarian cancer may be associated with the different changes i n their glycosylation. Of the many mechanisms that could explain these findings, a likely one is that a pathological process is removing API with triantennary chains from the circulation. In addition to their n ormal roles (API-enzyme inhibitor and Hp-transport protein) these prot eins are reported to have many other effects in biological systems, su ch as immunosuppression. As correct glycosylation of API and Hp is req uired for their normal stability/activity, changes in glycosylation co uld affect their functions in ovarian cancer and these modifications c ould alter the course of the disease.