Elevation of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer

Abstract

BACKGROUND Several investigators have revealed that urokinase‐type plasminogen activator (uPA) and its receptor (uPAR) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer. In this study, we examined whether the serum levels of uPA and uPAR could be used as predictors of the progression and prognosis of prostate cancer. METHODS Serum levels of uPA and uPAR in 54 healthy controls, 62 patients with benign prostatic hypertrophy (BPH), and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay. RESULTS The mean serum levels of uPA and uPAR in patients with prostate cancer were significantly higher than those in healthy controls and patients with BPH. Furthermore, the serum uPA and uPAR levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the serum levels of uPA and uPAR in patients with pathologically organ‐confined disease were significantly lower than in those with advanced disease. The overall survival rate of prostate cancer patients with elevated serum levels of either uPA or uPAR, or of both, was significantly lower than that of patients with normal serum levels of uPA and uPAR. CONCLUSIONS The results of this study indicate that the elevation of serum levels of either uPA or uPAR, or of both, could be used as new predictors of progression and prognosis in patients with prostate cancer. Prostate 39:123–129, 1999. © 1999 Wiley‐Liss, Inc.

The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth

“…We have addressed the possibility that cell surface bound complexes of uPA/uPAR regulate activation of PDGF-DD, partly as a result of a locally increased uPA concentration, but also by the prolonged and directed proteolytic activity of uPAR-bound uPA. Consistent with reports showing a prognostic value of uPA and uPAR in suggested PDGF-DD/PDGFRb driven pathologies such as prostate cancer (Miyake et al, 1999;Ustach and Kim, 2005), this proposed mechanism is likely to be beneficial for regulating the efficacy of PDGF-DD activation in the local milieu. Our results confirmed that the presence of uPAR increased PDGF-DD activation by uPA under certain conditions, but also showed that uPAR was not an absolute requirement for the activation to occur.…”

New circulating biomarkers for prostate cancer

“…Elevated circulating levels of uPA and uPAR have been linked to PCa stage and bone metastases. [68][69][70] In these studies, preoperative plasma uPA was a strong predictor of biochemical recurrence after surgery. Both preoperative uPA and uPAR were associated with features of aggressive biochemical recurrence such as development of distant metastasis suggesting an association with occult metastatic disease at time of local therapy.…”

Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies

“…Hashimoto et al (1998) demonstrated a significant correlation between the levels of MMP-7 mRNA in the primary prostate carcinoma and pathological stage and mean serum levels of uPA were reported to be significantly higher in patients with CaP compared to healthy individuals or patients with BPH (Miyake et al, 1999). However, no significant correlation was made in a study carried out to identify changes in blood plasma levels of MMP-1 between patients with CaP or with BPH (Lein et al, 1998).…”