Impaired Localization of Claudin-11 in Endometriotic Epithelial Cells Compared to Endometrial Cells

Abstract

Claudins are the major components of tight junctions and are often deregulated in human cancer, permitting escape of cancer cells along with the acquisition of invasive properties. Similarly, endometrial cells also show invasive capabilities; however, the role of tight junctions in endometriosis has only rarely been examined. In this study, we analyzed the protein expression and localization of claudin-7 and claudin-11 in human eutopic and ectopic endometrium and endometrial cell lines. We identified claudin-7 primarily at the basolateral junctions of the glandular epithelial cells in eutopic endometrium as well as in the ectopic lesions in nearly all glands and cysts. Quantification of claudin-7 localization by HSCORE showed a slight increase in peritoneal and deep infiltrating endometriosis (DIE) compared to eutopic endometrium. In contrast, claudin-11 was localized mainly in the apicolateral junctions in nearly all glandular epithelial cells of the eutopic endometrium. Interestingly, we observed a deregulation of claudin-11 localization to a basal or basolateral localization in ovarian ( P < .001), peritoneal ( P < .01), and DIE ( P < .05) and a moderately decreased abundance in ovarian endometriosis. In endometrial cell lines, claudin-7 was only present in epithelial Ishikawa cells, and silencing by small-interfering RNA increased cell invasiveness. In contrast, claudin-11 could be demonstrated in Ishikawa and endometriotic 12Z and 49Z cells. Silencing of claudin-11 decreased invasiveness of 12Z slightly but significantly in 49Z. We suggest that although claudin-7 and claudin-11 can be found in nearly all eutopic and ectopic epithelial cells, the impaired localization of claudin-11 in ectopic endometrium might contribute to the pathogenesis of endometriosis.

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

“…Up to now, only four studies were published regarding claudin expression in endometriosis with their findings summarized in Table 3 . In contrast to one study showing cycle-dependent differences of mRNA expression of claudins [ 80 ], three studies found no differences in expression of claudins-2–4 and 11 [ 83 , 84 , 85 , 86 ]. Again, no significant differences between the eutopic endometrium of women with and without endometriosis could be shown for claudins-2–4, 7, and 11 ( Table 3 ).…”

“…In contrast to claudins-2, 5, 7, and 11, which are not significantly different in the ectopic endometrium compared to eutopic endometrium [ 83 , 84 , 85 , 86 ], claudin-1 and claudin-4 are significantly different, showing a decreased protein presence in peritoneal endometriosis [ 83 ]. Furthermore, claudin-4 was found to also be different in ovarian endometriosis [ 84 , 85 ] ( Table 3 ).…”

“…In contrast to claudins-2, 5, 7, and 11, which are not significantly different in the ectopic endometrium compared to eutopic endometrium [ 83 , 84 , 85 , 86 ], claudin-1 and claudin-4 are significantly different, showing a decreased protein presence in peritoneal endometriosis [ 83 ]. Furthermore, claudin-4 was found to also be different in ovarian endometriosis [ 84 , 85 ] ( Table 3 ). Instead, data for claudin-3 are controversial; whereas Pan et al [ 84 ] found a reduced protein presence in ovarian endometriosis, Hoerscher et al [ 86 ] did not identify any changes, but in contrast identified claudin-3 expression in nearly all glands in the ectopic endometrium.…”

“…Although, for claudin-11, no differences in the HSCORE could be found between eutopic and ectopic endometrium, a significant switch of claudin-11 localization to a basal or basolateral localization in ovarian, peritoneal, and DIE could be observed [ 85 ]. In particular, in ovarian endometriosis, a shift to a more basal or basolateral localization was prominent compared to a preferential apicolateral localization in eutopic endometrium [ 85 ].…”

The Expression of CLDN11 in Invasive Ductal and Invasive Lobular Breast Cancer and Multivariate Prognostic Analysis

“…At the same time, it is also an essential part of the myelin sheath in the central nervous system, which plays a dual regulatory role in enhancing bone formation and inhibiting the occurrence of osteoclasts. Recently, CLDN11 has been reported to be down-regulated in some cancers, such as hepatocellular carcinoma, malignant melanoma, gastric cancer, or cutaneous squamous cell carcinoma 10 . Thus, CLDN11 has emerged as a hot area of cancer research.…”