Human kallikrein 2 (hK2), but not prostate-specific antigen (PSA), rapidlycomplexes with protease inhibitor 6 (PI-6) released from prostate carcinoma cells

Human kallikrein 2 (hK2) is a secreted, trypsin-like protease that shares 8 0% amino acid sequence identity with prostate-specific antigen (PSA). hK2 h as been shown to be a serum marker for prostate cancer and may also play a role in cancer progression and metastasis. We have previously identified a novel complex between human kallikrein 2 (hK2) and protease inhibitor 6 (PI -6) in prostate cancer tissue. PI-6 is an intracellular serine protease inh ibitor with both antitrypsin and antichymotrypsin activity. In the current study we have shown that PI-6 forms a rapid in vitro complex with hK2 but d oes not complex with PSA. Recombinant mammalian cells expressing both hK2 a nd PI-6 showed hK2-PI-6 complex in the spent media only after cell death an d lysis. Similarly LNCaP cells expressing endogenous hK2 and PI-6 showed ex tracellular hK2-PI-6 complex formation concurrently with cell death. Immuno staining of prostate cancer tissues with PI-6 monoclonal antibodies showed a marked preferential staining pattern in cancerous epithelial cells compar ed with noncancerous tissue. These results indicate that the hK2-PI-6 compl ex may be a naturally occurring marker of tissue damage and necrosis associ ated with neoplasia. Both hK2 and PI-6 were shed into the lumen of prostate cancer glands as granular material that appeared to be cellular necrotic d ebris. The differential staining pattern of P16 in tissues suggests a compl ex regulation of PI-6 expression that may play a role in other aspects of n eoplastic progression. (C) 2001 Wiley-Liss, Inc.