DECREASED BRANCHING, INCREASED FUCOSYLATION AND CHANGED SIALYLATION OF ALPHA-1-PROTEINASE INHIBITOR IN BREAST AND OVARIAN-CANCER

Proteolytic enzymes could be very important in spread of cancer, but t he role of the body's natural inhibitors of these enzymes in this proc ess is unknown. One such inhibitor is the serum glycoprotein, alpha-1- proteinase inhibitor (API). In previous studies we showed that the fuc ose-specific lectin, lotus tetragonolobus, extracted high amounts of A PI in cancer when patients were unresponsive to treatment. The aim of this study was to determine whether the carbohydrate structure of API is altered in cancer. API was isolated from the sera of healthy women and women with breast or ovarian cancer. By means of high-performance anion-exchange chromatography, cancer API was shown to contain more fu cose and less N-acetylglucosamine than healthy API. Further investigat ion of the purified specimens using a lectin-binding assay suggested t hat the cancer API was less branched and contained more alpha 2-6 and less alpha 2-3 sialic acid. Observations from both methods were consis tent with an increase in bi-antennary chains terminating in alpha 2-6 sialic acid and possibly more alpha 1-6 fucose in the core of the unit . These distinctive changes could have important consequences for the function of API in cancer and may help to develop more precise markers for monitoring pathological progression in this disease.