Associations of IgG N-linked oligosaccharide chains and proteases in sera of prostate cancer patients with and without alpha2-macroglobulin deficiency.

We previously reported on a number of cases of metastatic prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than 20 mg/dl (alpha2M deficiency). All PCa patients with alpha2M deficiency had multiple bone metastases. Proteases in ten PCa patients with and without alpha2M deficiency were studied and compared against ten healthy controls in order to elucidate the relationships between changes in sugar chain structure and neoplasia. We assessed the relationship between ratios of Fr4 to Fr1 and Fr2 (Fr4/Fr1+Fr2 ratios) of oligosaccharide chains, and ratios of free prostate-specific antigen (PSA) to total PSA (F/T ratios), and serum levels of matrix-metalloproteinase-2 (MMP-2) in PCa progression. Measurement of serum alpha2M concentration was performed by laser nephelometry. Serum PSA and MMP-2 levels were determined by enzyme immunoassay and free PSA by radioimmunoassay. N-linked oligosaccharides of human serum immunoglobulin G were analyzed using fluorophore-associated carbohydrate electrophoresis. In those PCa patients with alpha2M deficiency: (a) serum alpha2M and F/T ratios were lower (P<0.05) and (b) Fr4/Fr1+Fr2 ratios and serum MMP-2 levels were higher when compared with those PCa patients without alpha2M deficiency. There was a significant correlation between Fr4/Fr1+Fr2 ratios and F/T ratios or serum MMP-2 levels in PCa with alpha2M deficiency (P<0.05). Therefore, these markers may serve as an auxiliary serum tumor marker for monitoring of the bone metastases or progression of disease in PCa. (c) 2009 Wiley-Liss, Inc.