Publication
Title
In vitro and in situ activity-based labeling of fibroblast activation protein with UAMC1110-derived probes
Author
Abstract
Fibroblast activation protein (FAP) is a proline-selective protease that belongs to the S9 family of serine proteases. It is typically highly expressed in the tumor microenvironment (TME) and especially in cancer-associated fibroblasts, the main cell components of the tumor stroma. The exact role of its enzymatic activity in the TME remains largely unknown. Hence, tools that enable selective, activity-based visualization of FAP within the TME can help to unravel FAP’s function. We describe the synthesis, biochemical characterization, and application of three different activity-based probes (biotin-, Cy3-, and Cy5-labeled) based on the FAP-inhibitor UAMC1110, an in-house developed molecule considered to be the most potent and selective FAP inhibitor available. We demonstrate that the three probes have subnanomolar FAP affinity and pronounced selectivity with respect to the related S9 family members. Furthermore, we report that the fluorescent Cy3- and Cy5-labeled probes are capable of selectively detecting FAP in a cellular context, making these chemical probes highly suitable for further biological studies. Moreover, proof of concept is provided for in situ FAP activity staining in patient-derived cryosections of urothelial tumors.
Language
English
Source (journal)
Frontiers in Chemistry
Publication
2021
ISSN
2296-2646
DOI
10.3389/FCHEM.2021.640566
Volume/pages
9 (2021) , 12 p.
Article Reference
640566
ISI
000644960300001
Pubmed ID
33996747
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Development of tools and methods for the evaluation of FAP as a predictive/prognostic biomarker in cancer.
Infla-Med: Fundamental and translational research into targets for the treatment of inflammatory diseases.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 16.04.2021
Last edited 02.10.2024
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