Expression and distribution of cannabinoid receptors CB1 and CB2 in endometrial cancer


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Thangesweran Ayakannu1, Anthony Taylor1, Timothy Marczylo2, Jonathan Willets1, Quentin Davies3, Laurence Brown4, Esther Moss3, Justin Konje1
1Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK, 2Centre for Radiation, Chemical and Environtment Hazards, Public Health England, Harwell Campus, Oxfordshire, UK, 3University Hospitals of Leicester, NHS Trust, Gynaecology Oncology Department, Leicester, UK, 4University Hospitals of Leicester, NHS Trust, Pathology Department, Leicester, UK

Background

Endometrial cancer is the most common gynaecology in the UK, however, the aetiology of this disease remains complicated. Of the various compounds or factors thought to be involved in endometrial cancer development are the endocannabinoids that bind to and activate the endometrial cannabinoid receptors CB1 and CB2. This study aims at examining the role of these genes in endometrial cancer by analysing the difference in gene mRNA expression and distribution pattern, in normal and malignant endometrium.

Method

Endometrial cancer (n=21), adjacent background (n=14) and normal age-matched atrophic control tissues biopsies (n=6), were obtained at hysterectomy and stored in RNAlater. CB1 and CB2 transcript levels were determined using Taqman multiplex qRT-PCR (in triplicate) and normalised against the housekeeping genes, peptidylprolyl isomerase A (PPIA), mitochondrial ribosomal protein L19 (MRPL19) and importin 8 (IPO8). The distribution of CB1 and CB2 was shown using, immunohistochemistry with isotype specific antibodies.

Results

In the endometrial cancer tissues, CB1 (P < 0.001) and CB2 (P < 0.0042) mRNA relative expression levels were significantly decreased when compared to the atrophic tissues. Similarly CB1 and CB2 showed differential localisation patterns within the stromal and glandular components of the endometrial tissues, with a clear loss of CB1 immunoreactive protein from the luminal epithelial cell and stronger staining in the deeper glands. CB2 immunoreactivity was variable when compared against the atrophic, background and tumour tissues, but consistently lower in the tumour.

Conclusion

The results from this study support the hypothesis that down regulation of CB1 and CB2 receptors may be involved in the aetiopathology of endometrial cancer. It is hoped that innovative targeting of the endocannabinoid receptors may contribute to a novel tumour-suppressive treatment strategy for endometrial cancers.