Celtarys Adenosine Receptor fluorescent ligands as potent tools for the study of cancer specific GPCRs

The ONCOMET group from the Health Research Institute of Santiago led by Dr. Miguel Abal has published an interesting article showing tumor and stromal-specific genetic signatures and identifying A2BAR as a potential target in colorectal cancer. They performed A2BAR labelling in living cells and in complex 3D cellular models using Celtarys novel fluorescent GPCR ligands. 

The work, conducted by Dr. Jorge Barbazán with the collaboration of Dr. Jose Brea from Biofarma group and Dr. Eddy Sotelo, from ComBioMed group at the University of Santiago de Compostela, highlights the advantages of using fluorescent probes for monitoring GPCRs in living cells and for the development of new screening assays to identify and validate novel targeted therapies against cancer. Our CSO Maria Majellaro collaborated also in the article. 

Congratulations to the authors for this achievement! 

Abstract: 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.

Link of interest: https://www.sciencedirect.com/science/article/pii/S0753332222007971?utm_campaign=STMJ_AUTH_SERV_PUBLISHED&utm_medium=email&utm_acid=95574654&SIS_ID=&dgcid=STMJ_AUTH_SERV_PUBLISHED&CMX_ID=&utm_in=DM279002&utm_source=AC_