Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium

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This study compared EMT marker expression in endometriosis and endometrium, finding distinct upregulation of N-cadherin, Twist, and Snail in endometriosis lesions.

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This study investigated epithelial–mesenchymal transition (EMT) marker expression by assessing E-cadherin, N-cadherin, Twist, Snail, and Slug in peritoneal, ovarian, and rectovaginal endometriotic lesions (n=27) and endometrium (n=13) using immunohistochemistry, with additional reverse transcription PCR in tissue samples and primary cell cultures of endometriotic lesions (n=9) and endometrium (n=8). E-cadherin, N-cadherin, Twist, Snail, and Slug were expressed at both protein and mRNA levels in both tissues, but E-cadherin was stronger in epithelial cells while occasional E-cadherin-negative cells were more frequent in endometriosis. Compared with endometrium, endometriosis showed upregulated N-cadherin, Twist, and Snail, with inverse correlation between E- and N-cadherin and positive correlation between N-cadherin and Twist. This paper includes modest sample sizes and descriptive biomarker comparisons rather than direct functional testing of EMT. This paper is centrally about endometriosis — it compares EMT marker regulation in endometriotic lesions versus endometrium, indicating EMT may be regulated differently in endometriosis.

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Abstract

PURPOSE: Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug. METHODS: Immunohistochemistry was used for peritoneal, ovarian and rectovaginal endometriotic lesions (n = 27) and endometrium (n = 13). Reverse transcription polymerase chain reaction was applied to tissue samples and primary cell cultures of endometriotic lesions (n = 9) and endometrium (n = 8). RESULTS: In endometriosis and endometrium E-cadherin, N-cadherin, Twist, Snail and Slug were expressed on protein and mRNA level. E-cadherin expression was strong in epithelial cells, but single E-cadherin-negative cells were frequently present in endometriosis. In endometriosis N-cadherin, Twist and Snail expression were upregulated in comparison with endometrium. The expression of E- and N-cadherin was inversely correlated, while that of N-cadherin and Twist was positively correlated. CONCLUSION: This study strongly suggests that EMT may be regulated differently in endometriosis and the endometrium. Future research should further elucidate the regulation of EMT in the endometrium and endometriosis.
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Abstract

Purpose Epithelial–mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug.

Methods

Immunohistochemistry was used for peritoneal, ovarian and rectovaginal endometriotic lesions (n = 27) and endometrium (n = 13). Reverse transcription polymerase chain reaction was applied to tissue samples and primary cell cultures of endometriotic lesions (n = 9) and endometrium (n = 8).

Results

In endometriosis and endometrium E-cadherin, N-cadherin, Twist, Snail and Slug were expressed on protein and mRNA level. E-cadherin expression was strong in epithelial cells, but single E-cadherin-negative cells were frequently present in endometriosis. In endometriosis N-cadherin, Twist and Snail expression were upregulated in comparison with endometrium. The expression of E- and N-cadherin was inversely correlated, while that of N-cadherin and Twist was positively correlated.

Conclusion

This study strongly suggests that EMT may be regulated differently in endometriosis and the endometrium. Future research should further elucidate the regulation of EMT in the endometrium and endometriosis. Similar content being viewed by others

References

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Nat Cell Biol 2:76–83 Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A (2003) The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 116:499–511 Comijn J, Berx G, Vermassen P et al (2001) The two-handed E box binding zinc finger protein SIP1 down-regulates E-cadherin and induces invasion. Mol Cell 7:1267–1278 Aybar MJ, Nieto MA, Mayor R (2003) Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. Development 130:483–494 Acknowledgments The authors would like to acknowledge Dr. C. Gericke for statistical advice and Aidan Bartley for editorial advice. This research was funded by the Charité Universitätsmedizin without the involvement of other organizations. Conflict of interest None. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Bartley, J., Jülicher, A., Hotz, B. et al. Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium. Arch Gynecol Obstet 289, 871–881 (2014). https://doi.org/10.1007/s00404-013-3040-4 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-013-3040-4

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Condition tags

endometriosis

MeSH descriptors

Cadherins Endometriosis Endometrium Epithelial-Mesenchymal Transition Transcription Factors Twist-Related Protein 1 Adult Cadherins Cadherins Cell Nucleus Cell Nucleus Cells, Cultured Cytoplasm Cytoplasm Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium

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