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Front. Pharmacol. | doi: 10.3389/fphar.2018.00431

GPCRomics: GPCR expression in cancer cells and tumors identifies new, potential biomarkers and therapeutic targets

Paul A. Insel1, 2*,  Krishna Sriram1, Shu Z. Wiley1, Andrea Wilderman1, Trishna Katakia1, Thalia McCann1, Hiroshi Yokouchi1,  Lingzhi Zhang1,  Ross Corriden1, Dongling Liu1,  Michael Feigin3, Randall P. French4, Andrew M. Lowy4 and Fiona Murray1, 2, 5
  • 1Pharmacology, University of California, San Diego, United States
  • 2Medicine, University of California, San Diego, United States
  • 3Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, United States
  • 4Departments of Medicine and Surgery and Moores Cancer Center, University of California, San Diego, United States
  • 5School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, United Kingdom

G protein-coupled receptors (GPCRs), the largest family of targets for approved drugs, are rarely targeted for cancer treatment, except for certain endocrine and hormone-responsive tumors. Limited knowledge regarding GPCR expression in cancer cells likely has contributed to this lack of use of GPCR-targeted drugs as cancer therapeutics. We thus undertook GPCRomic studies to define the expression of endoGPCRs (which respond to endogenous hormones, neurotransmitters, and metabolites) in multiple types of cancer cells. Using TaqMan qPCR arrays to quantify the mRNA expression of ~340 such GPCRs, we found that human chronic lymphocytic leukemia (CLL) cells/stromal cells associated with CLL, breast cancer cell lines, colon cancer cell lines, pancreatic ductal adenocarcinoma (PDAC) cells, cancer associated fibroblasts (CAFs), and PDAC tumors express 50 to >100 GPCRs, including many orphan GPCRs (which lack known physiologic agonists). Limited prior data exist regarding the expression or function of most of the highly expressed GPCRs in these cancer cells and tumors. Independent results from cancer databases confirm the expression of such GPCRs. We propose that highly expressed GPCRs in cancer cells (for example, GPRC5A in PDAC and colon cancer cells and GPR68 in PDAC CAFs) may contribute to the malignant phenotype, serve as biomarkers and/or may be novel therapeutic targets for the treatment of cancer.

Keywords: breast cancer, Cancer microenvironment, chronic lymphocytic leukemia, Colon Cancer, GPCR array, Orphan receptors, Pancreatic Cancer

Received: 06 Feb 2018; Accepted: 12 Apr 2018.

Edited by:

Ramaswamy Krishnan, Beth Israel Deaconess Medical Center, Harvard Medical School, United States

Reviewed by:

Kevin D. Pfleger, Harry Perkins Institute of Medical Research, Australia
Deepak A. Deshpande, Thomas Jefferson University, United States  

Copyright: © 2018 Insel, Sriram, Wiley, Wilderman, Katakia, McCann, Yokouchi, Zhang, Corriden, Liu, Feigin, French, Lowy and Murray. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Paul A. Insel, University of California, San Diego, Pharmacology, San Diego, United States,