RT Journal Article
T1 Identification of A2BAR as a potential target in colorectal cancer using novel fluorescent GPCR ligands
A1 Barbazán García, Jorge
A1 Majellaro, Maria
A1 Martínez Rodríguez, Antón Leandro
A1 Brea Floriani, José Manuel
A1 Sotelo Pérez, Eddy
A1 Abal Posada, Miguel
K1 Colorectal cancer
K1 GPCRs
K1 Adenosine receptors
K1 Tumor microenvironment
K1 Fluorescent ligands
K1 Drug screening
AB G-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 methodologies
PB Elsevier
YR 2022
FD 2022-07-18
LK https://hdl.handle.net/10347/45091
UL https://hdl.handle.net/10347/45091
LA eng
NO Jorge 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.2022.113408
NO This work was supported by the Juan de la Cierva grant program to Jorge Barbazán (IJC2018-036875-I) and CIBERONC (CB16/12/00328). We also thank the Consellería de Cultura, Educación e Ordenación Universitaria of the Galician Government (grant: ED431B 2020/43), Centro Singular de Investigación de Galicia accreditation 2019–2022 (ED431G 2019/03) and the European Regional Development Fund (ERDF), Ministerio de Ciencia e Innovación-Agencia Estatal de Investiogación-FEDER-EU (PID2021-124010OB-100) for the financial support
DS Minerva
RD 3 may 2026