T-cadherin inhibits invasion and migration of endometrial stromal cells in endometriosis

Abstract

STUDY QUESTION What is the expression level of T-cadherin in endometriosis, and does T-cadherin play a role in regulating invasion and migration of endometrial stromal cells? SUMMARY ANSWER T-cadherin expression was reduced in ectopic endometriotic lesions compared to eutopic endometrium, and T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells. WHAT IS KNOWN ALREADY Endometriosis is a disease that involves active cell invasion and migration. T-cadherin can inhibit cell invasion, migration and proliferation in various cancer cells, but its role in endometriosis has not been investigated. STUDY DESIGN, SIZE, DURATION We explored the expression status of T-cadherin in 40 patients with and 24 without endometriosis. We also isolated endometrial stromal cells to study the invasion, migration and signaling pathway regulation of T-cadherin overexpression. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were recruited at the Guangzhou Women and Children’s Medical Center to study the expression levels of T-cadherin. The expression of T-cadherin was detected by immunohistochemistry staining and western blot. H-score was used to evaluate the staining intensity of T-cadherin. The correlation between T-cadherin expression levels (H-score) and endometriosis patients’ age, stage, lesion size and adhesion was analyzed. Endometrial stromal cells from patients with and without endometriosis were isolated, and cell invasion and migration were detected by transwell assays after T-cadherin overexpression. The expression of vimentin in T-cadherin-overexpressed cells was detected by western blot. After T-cadherin overexpression, the phosphorylation profile of signaling pathway proteins was detected with the Proteome Profiler Human Phospho-Kinase Array Kit. MAIN RESULTS AND THE ROLE OF CHANCE There was no difference in the expression of T-cadherin in the normal endometrium of control patients and the eutopic endometrium of endometriotic patients, but it was significantly decreased in the ectopic endometrium of endometriotic patients, compared with control endometrium and eutopic endometrium of endometriosis patients (P < 0.0001, for both). Western blot analysis also showed that the expression of T-cadherin was decreased in ectopic endometriotic lesions, but not the normal control endometrium or the endometriotic eutopic endometrium. The results of transwell assays indicated that T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells. In addition, T-cadherin overexpression promoted the phosphorylation of HSP27 (S78/S82) and JNK 1/2/3 (T183/Y185, T221/Y223) and decreased the expression of vimentin, MMP2 and MMP9 in eutopic endometriosis stromal cells. LARGE-SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The control group were patients with benign gynecological conditions (e.g. uterus myoma, endometrial or cervical polyp), which may have genetic or epigenetic variations associated with T-cadherin expression and signaling pathways. The case numbers of involved endometriosis and control patients were limited. This study only used endometrial stromal cells from patients with or without endometriosis. Ideally, ectopic endometrial stromal cells of the ovarian endometriotic lesions should also be utilized to explore the function of T-cadherin. WIDER IMPLICATIONS OF THE FINDINGS Further investigation of the role of T-cadherin in endometriosis may generate new potential therapeutic targets for this complex disorder. STUDY FUNDING AND COMPETING INTEREST(S) This study was supported by the Natural Science Foundation of Guangdong Province (2016A030313495), National Natural Science Foundation of China (81702567, 81671406, 31871412), the Science and Technology Programs of Guangdong (2017A050501021), Medical Science Technology Research Fund of Guangdong Province (A2018075), the Science and Technology Programs of Guangzhou City (201704030103), Internal Project of Family Planning Research Institute of Guangdong Province (S2018004), Post-doc initiation fund of Guangzhou (3302) and Post-doc science research initiation fund of Guangzhou Women and Children’s Medical Center (20160322). There are no conflicts of interest.

The Endometriotic Nodule Has Lower T-cadherin, E-cadherin, Progesterone Receptor and Oestrogen Receptor Than Endometrioma Tissue

“…In the same study, 40 endometriosis tissues were examined, and it was not clearly stated how many of these tissues were DIE tissues. In the cell culture phase of the study, it was shown that T-cadherin inhibits invasion and migration of endometrial stromal cells in endometriosis [21]. In the current study, E-cadherin level was found to be low in endometriotic nodule tissue, in accordance with the literature.…”

“…In the literature examining T-cadherin level in endometriosis tissue, T-cadherin level was found to be low in endometriosis tissue [21]. It was shown that the expression of E-cadherin was decreased in endometriotic nodule tissue [22].…”

“…In the single study that investigated the T-cadherine levels in endometriosis tissue in literature it was reported that the decreased T-cadherine expression may be linked to progesterone resistance but noticed that it was a subject of future studies [21].…”

T-cadherin in epithelial ovarian cancer: relationship with cancer progression and drug resistanceT-cadherin in epithelial ovarian cancer: relationship with cancer progression and drug resistance

“…T-cadherin regulates cell migration and target nding by reducing homologous and heterophilic interactions involved in adhesion [21]. Downregulation of T-cadherin has been implicated in the progression of various carcinomas [22]. The upregulation of T-cadherin reduces the malignant characteristics of human prostate cancer, melanoma, breast cancer and liver cancer cell lines.…”

Iron-Storage Protein Ferritin Is Upregulated in Endometriosis and Iron Overload Contributes to a Migratory Phenotype

“…Endometriosis is not a cancerous disease, but endometriotic lesions have cancer-like traits, including cell invasion and migration [16]. Endometriotic epithelial cell lines, such as 12Z, have shown enhanced migratory potential compared to normal endometrial epithelial cells [17].…”