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Int J Cancer. 2018 Jan 1;142(1):121-132. doi: 10.1002/ijc.31030. Epub 2017 Sep 21.

G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1.

Author information

1
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
2
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
3
Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria.
4
UCL Cancer Institute, University College London, London, United Kingdom.
5
Institute of Clinical Pharmacology, Goethe University, Frankfurt/Main, Germany.
6
Institute of Pathology, Medical University of Graz, Graz, Austria.
7
Department of Pathology, Otto von Guericke University, Magdeburg, Germany.
8
BioTechMed, Graz, Austria.

Abstract

The putative cannabinoid receptor GPR55 has been shown to play a tumor-promoting role in various cancers, and is involved in many physiological and pathological processes of the gastrointestinal (GI) tract. While the cannabinoid receptor 1 (CB1 ) has been reported to suppress intestinal tumor growth, the role of GPR55 in the development of GI cancers is unclear. We, therefore, aimed at elucidating the role of GPR55 in colorectal cancer (CRC), the third most common cancer worldwide. Using azoxymethane (AOM)- and dextran sulfate sodium (DSS)-driven CRC mouse models, we found that GPR55 plays a tumor-promoting role that involves alterations of leukocyte populations, i.e. myeloid-derived suppressor cells and T lymphocytes, within the tumor tissues. Concomitantly, expression levels of COX-2 and STAT3 were reduced in tumor tissue of GPR55 knockout mice, indicating reduced presence of tumor-promoting factors. By employing the experimental CRC models to CB1 knockout and CB1 /GPR55 double knockout mice, we can further show that GPR55 plays an opposing role to CB1 . We report that GPR55 and CB1 mRNA expression are differentially regulated in the experimental models and in a cohort of 86 CRC patients. Epigenetic methylation of CNR1 and GPR55 was also differentially regulated in human CRC tissue compared to control samples. Collectively, our data suggest that GPR55 and CB1 play differential roles in colon carcinogenesis where the former seems to act as oncogene and the latter as tumor suppressor.

KEYWORDS:

CB1; CNR1; GPR55; colorectal carcinogenesis

PMID:
28875496
PMCID:
PMC5679368
[Available on 2019-01-01]
DOI:
10.1002/ijc.31030
[Indexed for MEDLINE]

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