Detection of increased extracellular release and sequestering of latent, active, and inactive forms of prostatic kallikreins (e.g. free and complexed PSA and hK2) provide extremely sensitive means to detect changes in tissue architecture that accompany progression and invasion of prostate cancer lesions at an early stage. Recent studies from our laboratory demonstrate that there are significantly elevated levels of various PSA- and hK2-forms in blood up to 20 years before men are diagnosed with clinically significant prostate cancer. The magnitude of extracellular release of active and latent protease-forms parallels invasion and progression of prostate cancer, and results in the activation of specific cascades that modify local regulatory target proteins in the extracellular microenvironment of prostate cancer lesions.
