Ayakannu Thangesweran, Taylor Anthony H, Konje Justin C
a Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine , University of Leicester , Leicester , UK.
b Department of Gynaecology Oncology , Royal Surrey County Hospital , Guildford , UK.
J Recept Signal Transduct Res. 2018 Oct-Dec;38(5-6):385-392. doi: 10.1080/10799893.2018.1531890. Epub 2018 Dec 20.
The lack of good diagnostic/prognostic biomarkers and the often late presentation of endometrial cancer (EC) hinders the amelioration of the morbidity and mortality rates associated with this primarily estrogen-driven disease, a disease that is becoming more prevalent in the population. Previous studies on the expression of the classical cannabinoid receptors, CB1 and CB2, suggest these could provide good diagnostic/prognostic biomarkers for EC but those observations have been contradictory. In this study, we sought to resolve the inconsistency of CB1 and CB2 expression levels in different EC studies. To that end, we used qRT-PCR and immunohistochemistry (IHC) for CB1 and CB2 in endometrial biopsies from women with or without EC and found that transcript levels for both CB1 and CB2 were significantly decreased by 90 and 80%, respectively in EC. These observations were supported by histomorphometric studies where CB1 and CB2 staining intensity was decreased in all types of EC. These data suggest that the loss of both types of CB receptors is potentially involved in the development of or progression of EC and that CB1 and CB2 receptor expression could serve as useful histological markers and therapeutic targets in the treatment of or prevention of EC.
缺乏良好的诊断/预后生物标志物以及子宫内膜癌(EC)通常出现较晚,这阻碍了与这种主要由雌激素驱动的疾病相关的发病率和死亡率的改善,而这种疾病在人群中越来越普遍。先前关于经典大麻素受体CB1和CB2表达的研究表明,它们可为EC提供良好的诊断/预后生物标志物,但这些观察结果相互矛盾。在本研究中,我们试图解决不同EC研究中CB1和CB2表达水平的不一致问题。为此,我们对有或无EC的女性子宫内膜活检组织中的CB1和CB2进行了qRT-PCR和免疫组织化学(IHC)检测,发现EC中CB1和CB2的转录水平分别显著降低了90%和80%。组织形态计量学研究支持了这些观察结果,即所有类型的EC中CB1和CB2的染色强度均降低。这些数据表明,两种类型的CB受体缺失可能与EC的发生或进展有关,并且CB1和CB2受体表达可作为治疗或预防EC的有用组织学标志物和治疗靶点。