TY  - JOUR
A1  - Dreymann, Nico
A1  - Wuensche, Julia
A1  - Sabrowski, Wiebke
A1  - Moeller, Anja
A1  - Czepluch, Denise
A1  - Vu Van, Dana
A1  - Füssel, Susanne
A1  - Menger, Marcus M.
T1  - Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA
T2  - International journal of molecular sciences
N2  - Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K-D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K-D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity.
KW  - biomarker
KW  - cancer
KW  - cancer therapy
KW  - DNA aptamer
KW  - microscale thermophoresis (MST)
KW  - SELEX
KW  - surface plasmon resonance spectroscopy (SPR)
KW  - uPA
KW  - uPAR
KW  - urokinase
Y1  - 2022
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/63586
SN  - 1661-6596
SN  - 1422-0067
VL  - 23
IS  - 9
PB  - MDPI
CY  - Basel
ER  -