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.