Reduced proliferation and cell adhesion in endometriosis

Scotti, Silvestro; Regidor, Pedro‐Antonio; Schindler, A. E.; Winterhager, E.

doi:10.1093/molehr/6.7.610

Cited by 65 publications

(51 citation statements)

References 34 publications

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“…In agreement with other studies, no difference of proliferation rate was seen in endometrium from patients with vs. without endometriosis (34). Interestingly, significantly reduced proliferation activity was observed in endometriosis compared with endometrium.…”

Section: Discussionsupporting

confidence: 92%

Reduction of apoptosis and proliferation in endometriosis

Béliard

Noël

Foidart

2004

Fertility and Sterility

149

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Objective: To evaluate whether endometriosis could be related to an impaired balance between apoptosis and proliferation, two processes which could be modulated by hormonal status.Design: Immunohistochemical study.Setting: Academic research laboratory. Intervention(s):Endometriotic samples obtained from peritoneum of women aged 26-40 years who were undergoing laparoscopy for pain or infertility. Main Outcome Measure(s):Apoptotic cells were detected with the use of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The production of p53 and bcl-2, estrogen and Progesterone (P) receptors, and cellular proliferation were assessed by immunohistochemistry in eutopic and ectopic endometria from 30 patients with endometriosis throughout the menstrual cycle. Results were compared with those from normal endometria from 15 fertile patients. Result(s):Endometriotic lesions were characterized by reduced TUNEL and p53 stainings and by enhanced bcl-2 staining. No correlation between apoptosis and estrogen receptor or P receptor levels was found. A lower amount of steroid receptor was found in endometriotic tissues, without cyclic modulation, compared with the eutopic endometrium. Conclusion(s):Our results suggest that when endometrial tissue is located at ectopic locations, it differs from eutopic endometrium by its proliferation rate, steroid hormone levels, and markers of apoptosis. A reduced sensitivity of endometriotic cells to apoptosis could promote the dissemination and implantation of these cells to ectopic sites.

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Section: Discussionsupporting

confidence: 92%

Reduction of apoptosis and proliferation in endometriosis

Béliard

Noël

Foidart

2004

Fertility and Sterility

149

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“…Previous studies have shown that while proliferative activity is reduced in endometriotic lesions compared with eutopic endometria, 40 red endometriotic lesions, known to be relatively active, have high proliferative activity compared with black lesions, which are more established and matured. 25,41 These findings suggest that the status of lesions correlate with the mitogenic activity.…”

Section: Fkbp52 Deficiency Promotes Endometriotic Growth and Cell Promentioning

confidence: 93%

Deficiency of Immunophilin FKBP52 Promotes Endometriosis

Hirota

Tranguch

Daikoku

et al. 2008

The American Journal of Pathology

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Endometriosis is a common gynecological disease that affects approximately 10% of women of childbearing age. It is characterized by endometrial growth outside the uterus and often results in inflamed lesions, pain, and reduced fertility. Although heightened estrogenic activity and/or reduced progesterone responsiveness are considered to be involved in the etiology of endometriosis, neither the extent of their participation nor the underlying mechanisms are clearly understood. Heterogeneous uterine cell types differentially respond to estrogen and progesterone (P 4 ). P 4 , primarily acting via its nuclear receptor (PR), activates gene transcription and impacts many reproductive processes. Deletion of Fkbp52, an immunophilin cochaperone for PR, results in uterine-specific P 4 resistance in mice, creating an opportunity to study the unique aspects of P 4 signaling in endometriosis. Here we explored the roles of FKBP52 in this disease using Fkbp52 ؊/؊ mice. We found that the loss of FKBP52 encourages the growth of endometriotic lesions with increased inflammation , cell proliferation , and angiogenesis. We also found remarkable down-regulation of FKBP52 in cases of human endometriosis. Our results provide the first evidence corroborated by genetic studies in mice for a potential role of an immunophilin cochaperone in the etiology of human endometriosis. This investigation is highly relevant for clinical application , particularly because P 4 resistance is favorably indicated in endometriosis and other gynecological diseases.

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“…The molecular events of EMT include down-regulation of epithelial markers (e.g., E-cadherin) and overexpression of mesenchymal markers (e.g., fibronectin and vimentin), which involves activation of a number of transcription factors, including Snail, Slug, Twist, Zeb1, and SIP1. Existing evidences have showed invasive behavior and cytoskeletal rearrangement of endometrial epithelial cells during ectopic implantation concomitant with reduced expression of E-cadherin (6) and up-regulation of vimentin expression (7) in endometriotic lesions compared with normal uterine endometrium. These data implicate a possible role of EMT in adenomyosis development.…”

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confidence: 99%

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Zhou

et al. 2012

Molecular & Cellular Proteomics

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Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia, and infertility in 8.8 -61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a two-dimensional polyacrylamide gel electrophoresis/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial to mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial to mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a ␤-catenin/T-cell factor (Tcf) signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1␣/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis, and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

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Reduced proliferation and cell adhesion in endometriosis

Cited by 65 publications

References 34 publications

Reduction of apoptosis and proliferation in endometriosis

Reduction of apoptosis and proliferation in endometriosis

Deficiency of Immunophilin FKBP52 Promotes Endometriosis

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

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