Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands

Barbazán García, JorgeMajellaro, MariaMartínez Rodríguez, Antón LeandroBrea Floriani, José ManuelSotelo Pérez, EddyAbal Posada, Miguel2026-01-132026-01-132022-07-18Jorge Barbazán, Maria Majellaro, Antón L. Martínez, José M. Brea, Eddy Sotelo, Miguel Abal, Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands, Biomedicine & Pharmacotherapy, Volume 153, 2022, 113408, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.113408https://hdl.handle.net/10347/45091G-protein coupled receptors (GPCRs) have been largely targeted in a wide range of diseases, but few therapies have been directed against GPCRs in the field of cancer, partly because of the lack of effective target identification strategies. Here, using colorectal cancer (CRC) as a model, we explored the gene expression of a panel of GPCRs in tumor and stromal cells, identifying specific gene sets defining each cellular compartment. We selected the adenosine receptor 2B (A2BAR), specifically expressed in cancer cell lines compared with stromal cells, to explore the use of fluorescent ligands that can be used for target visualization. Fluorescent probes allowed semi-quantitative receptor mapping in living cells and validated the specific expression of A2BAR in CRC cell lines. As well, fluorescent ligands were effective at monitoring real-time A2BAR receptor labeling using live-imaging modalities, and displayed high efficiency when used to label complex 3D cellular systems such as tumor spheroids. Finally, we validated A2BAR as a potential pharmacological tool in CRC, using selective antagonists, finding a reduction in tumor cell proliferation. This proof-of-concept study suggests the use of fluorescent ligands for GPCR characterization through imaging, and as possible new tools used for target validation in drug screening methodologieseng© 2022 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND licenseAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Colorectal cancerGPCRsAdenosine receptorsTumor microenvironmentFluorescent ligandsDrug screeningIdentification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligandsjournal article10.1016/j.biopha.2022.1134081950-6007open access