Differential glycosylation of cellular prostate specific antigen and the regulatory mechanism of its secretion

Although serum prostate specific antigen (PSA), derived from cellular PSA t hrough secretion, is widely used as a marker for prostate cancer (CAP), the exact regulatory mechanism of its secretion is not fully understood. To ex plore the regulation of serum PSA concentration, we examined whether the gl ycosylation state of cellular PSA might be associated with its secretion, t hus determining its serum concentration. Blood and prostate tissue specimen s were obtained from patients undergoing radical prostatectomy, Following p reparation of cell extracts by tissue homogenization, the concentrations of serum and cellular PSA were determined using the Tandem-E PSA kit. The ext ent of cellular PSA glycosylation was then assessed by Western blot and aff inoblott analyses. Neither serum nor cellular PSA concentrations correlated with the Gleason scores. Similarly, no direct relation between serum and c ellular PSA levels was observed. However, the Western blots showed that the cellular PSA proteins were converted to the deglycosylated forms with glyc osidase treatment, indicating differential glycosylation of cellular PSA, A ffinoblotting further revealed that the various amounts of PSA glycosylatio n were associated with the serum PSA levels, with an inverse correlation be tween serum PSA and cellular PSA glycosylation: the greater the PSA glycosy lation, the lower the serum PSA, and vice versa, The present study demonstr ates that cellular PSAs in CAP specimens are differentially glycosylated an d that such difference correlates well with the serum PSA concentration. Th erefore, the concentrations of serum PSA appear to depend in part on a sele ctive secretion of cellular PSA, which could be regulated primarily by its glycosylation state.