The prostate-localized kallikreins: Prostate specific antigen and human kallikrein 2

Prostate specific antigen (PSA) and human kallikrein 2 (hK2) are closely related serine proteases localized primarily in the prostate gland. Despite the molecular similarities of the two prostate kallikreins, recent studies have revealed striking differences between hK2 and PSA. Unlike the weak chymotrypsin-like activity exhibited by PSA, hK2 is a potent trypsin-like enzyme with more than 20,000-fold relative higher enzyme activity than PSA on peptide substrates. The inactive precursor form of PSA, proPSA, is converted efficiently to active PSA by hK2 suggesting an important in vivo regulatory role for hK2 on PSA activity. The high homology between hK2 and PSA results in significant cross-reactivity to hK2 by polyclonal and some monoclonal antibodies to PSA. Monoclonal antibodies specific to hK2 with minimal cross- reactivity to PSA have been produced, allowing cell and serum analysis of hK2. Although the same secretory epithelial cells in the prostate produce both kallikreins, hK2 is more highly expressed in poorly differentiated cancer cells and is more tumor associated than PSA. Preliminary serum studies with immunoassays specific for hK2 indicate that serum hK2 in combination with total and free PSA provides increased specificity for prostate cancer.