The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

Abstract

In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5-10.5 months] vs. not reached, p < 0.

Markers of Cancer Cell Invasion: Are They Good Enough?

“…One of the main systems responsible for ECM proteolysis is the plasminogen activation system that triggers a powerful serine protease, plasmin. The central component of this system is the uPA and its receptor (uPAR), the interaction of which stimulates proteolysis of plasminogen to plasmin [135,136]. uPA is believed to play a significant role in tumor invasion and metastasis [135,136,137].…”

“…The central component of this system is the uPA and its receptor (uPAR), the interaction of which stimulates proteolysis of plasminogen to plasmin [135,136]. uPA is believed to play a significant role in tumor invasion and metastasis [135,136,137]. Experiments in model animals demonstrated that inhibition of uPA and/or the uPA/uPAR interaction slows down metastasis [135].…”

Thidiazuron decreases epithelial‐mesenchymal transition activity through the NF‐kB and PI3K/AKT signalling pathways in breast cancer

“…29 invasion. [33][34][35] In this exploration, we found that TDZ inhibits con- Epithelial-mesenchymal transition take place during the untimely phases of the conversion of tumours into the malignant neoplasm. 44 The thought that EMT is allied with an progression of metastatic cancer cells is evidenced by the examination, which attainment of mesenchymal indicators, for example Snail, Vimentin and Twist by epithelial carcinoma cells is linked with augmented metastatic ability, [45][46][47] as is increased nuclear expression of β-catenin 9 and E-cadherin loss.…”

Explication of the roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) as diagnostic and predictor tools for prostate cancer in equivocal PSA range of 4–10 ng/mL

“…Previously, Crowley et al (1993) reported that a competitive analogue of uPA that inhibits binding of uPA with its receptor in vivo consequently inhibits metastasis in prostate cancer. Recently, serum uPA were found to be significantly elevated in breast cancer patients compared to non-malignant counterparts ( Banys-Paluchowski et al, 2019 ).…”