Expression of the putative cannabinoid receptor GPR55 is increased in endometrial carcinoma

Thangesweran Ayakannu,Anthony H Taylor,Justin C Konje

doi:10.1007/s00418-021-02018-4

Abstract

Although the expression of the putative cannabinoid receptor GPR55 has been shown to be involved in the growth of various tumours and is increased in a number of cancers, its expression has not been examined in patients with endometrial cancer (EC). Quantitative RT-PCR (for mRNA levels) and immunohistochemistry (for protein levels) were used to measure GPR55 expression in patients with Type 1 and Type 2 EC and correlated against cannabinoid receptor (CB1 and CB2) protein levels using non-cancerous endometrium as the control tissue. The data indicated that GPR55 transcript and GPR55 protein levels were significantly (p < 0.002 and p < 0.0001, respectively) higher in EC tissues than in control tissues. The levels of immunoreactive GPR55 protein were correlated with GPR55 transcript levels, but not with the expression of CB1 receptor protein, and were inversely correlated with CB2 protein expression, which was significantly decreased. It can be concluded that GPR55 expression is elevated in women with EC, and thus could provide a potential novel biomarker and therapeutic target for this disease.

Highlights

The incidence of endometrial cancer (EC) is increasing worldwide, especially in younger women (Lortet-Tieulent et al 2018)
GPR55 transcript levels were higher in the estrogen-independent Type 2 EC tumours (n = 6), this was not statistically significant (Fig. 1b, c)
We mapped out the expression pattern for GPR55 in both Type 1 and Type 2 EC and demonstrated that it was higher in the EC than in control samples and this increased expression was related to tumour type and grade, both at the transcript (p = 0.002) and protein (p < 0.0001) level

Summary

Introduction

The incidence of endometrial cancer (EC) is increasing worldwide, especially in younger women (Lortet-Tieulent et al 2018). The increased incidence in younger women has been linked to an increased abundance of food and the changes in metabolism (including obesity) associated with increased caloric intake (McDonald and Bender 2019), something that has been known for more than 50 years (Twombly et al 1961). The incidence of EC is increasing in younger women, it remains more prevalent in postmenopausal women, who have an increased caloric intake. One key player in the control of energy metabolism, is the membrane-derived ligand lysophosphatidylinositol (LPI), which binds avidly to the orphan G protein-coupled receptor GPR55 (Alhouayek et al 2018). LPI and its 2-arachidonyl derivative (2-arachidonyl-lysophosphatidylinositol; 2-ALPI) are considered the endogenous ligands for GPR55, other ligands, especially those of the endocannabinoid system (ECS), bind to or activate this receptor (Ryberg et al 2007)

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Results

Conclusion