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 the role of the body's natural inhibitors of these enzymes in this process is unknown. One such inhibitor is the serum glycoprotein, alpha-1-proteinase inhibitor (API). In previous studies we showed that the fucose-specific lectin, lotus tetragonolobus, extracted high amounts of API 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 fucose and less N-acetylglucosamine than healthy API. Further investigation of the purified specimens using a lectin-binding assay suggested that the cancer API was less branched and contained more alpha 2-6 and less alpha 2-3 sialic acid. Observations from both methods were consistent 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.
Goodarzi
M T
MT
Department of Clinical Biochemistry, Medical School, University of Newcastle Upon Tyne, UK.
Turner
G A
GA
D002288:Adenocarcinoma, Mucinous / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood*; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry; D003208:Concanavalin A / Q000378:metabolism; D005260:Female; D005643:Fucose / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood*; D010835:Phytohemagglutinins / Q000378:metabolism; D037121:Plant Lectins; D054788:Ribosome Inactivating Proteins; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000378:metabolism
D002241:Carbohydrates; D005936:Glucans; D037102:Lectins; D010835:Phytohemagglutinins; D037121:Plant Lectins; C050600:Sambucus nigra lectins; D015842:Serine Proteinase Inhibitors; D012794:Sialic Acids; D000515:alpha 1-Antitrypsin; C100156:leukoagglutinins, plants; D003208:Concanavalin A; D005643:Fucose; D054788:Ribosome Inactivating Proteins