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Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2

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Abstract

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)—enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation—appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean±SD positive cells: 24.3±28.3% and 69.3±12.1%), together with loss of MMP-3 expression (0 versus 17.5%±20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.

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References

  1. Birkedal-Hansen H, Moore WG, Bodden MK et al (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250

    CAS  PubMed  Google Scholar 

  2. Bruner-Tran KL, Eisenberg E, Yeaman GR, Anderson TA, McBean J, Osteen KG (2002) Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab 87:4782–4791

    Article  CAS  PubMed  Google Scholar 

  3. Bruse C, Bergqvist A, Carlstrom K, Fianu-Jonasson A, Lecander I, Astedt B (1998) Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women. Fertil Steril 70:821–826

    Article  CAS  PubMed  Google Scholar 

  4. Collette T, Bellehumeur C, Kats R, Maheux R, Mailloux J, Villeneuve M, Atloum A (2004) Evidence for an increase release of proteolytic activity by eutopic endometrial tissue in women with endometriosis and for involvement of MMP-9. Human Reprod 19:1257–1264

    Article  CAS  Google Scholar 

  5. Cox KE, Piva M, Sharpe-Timms KL (2001) Differential regulation of matrix metalloproteinase-3 gene expression in endometriotic lesions compared with endometrium. Biol Reprod 65:1297–1303

    CAS  PubMed  Google Scholar 

  6. Chung HW, Lee JY, Moon HS et al (2002) Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium. Fertil Steril 78:787–795

    Article  PubMed  Google Scholar 

  7. Curry TE Jr, Osteen KG (2001) Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol Reprod 64:1285–1296

    CAS  PubMed  Google Scholar 

  8. Darai E, Leblanc M, Walker-Combrouze F, Bringuier AF, Madelenat P, Scoazec JY (1998) Expression of cadherins and CD44 isoforms in ovarian endometrial cysts. Hum Reprod 13:1346–1352

    Article  CAS  PubMed  Google Scholar 

  9. di Nezza LA, Misajon A, Zhang J et al (2002) Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer 94:1466–1475

    Article  PubMed  Google Scholar 

  10. Fauvet R, Poncelet C, Hugol D, Lavaur A, Feldmann G, Darai E (2003) Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours. Virchows Arch 443:38–43

    Article  CAS  PubMed  Google Scholar 

  11. Gaetje R, Kotzian S, Herrmann G, Baumann R, Starzinski-Powitz A (1995) Invasiveness of endometriotic cells in vitro. Lancet 346:1463–1464

    Article  CAS  PubMed  Google Scholar 

  12. Gagne D, Rivard M, Page M et al (2003) Development of a nonsurgical diagnostic tool for endometriosis based on the detection of endometrial leukocyte subsets and serum CA-125 levels. Fertil Steril 80:876–885

    Article  PubMed  Google Scholar 

  13. Gilabert-Estelles J, Estelles A, Gilabert J et al (2003) Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis. Hum Reprod 18:1516–1522

    Article  CAS  PubMed  Google Scholar 

  14. Goffin F, Frankenne F, Beliard A et al (2002) Human endometrial epithelial cells modulate the activation of gelatinase a by stromal cells. Gynecol Obstet Invest 53:105–111

    Article  CAS  PubMed  Google Scholar 

  15. Jolicoeur C, Boutouil M, Drouin R, Paradis I, Lemay A, Akoum A (1998) Increased expression of monocyte chemotactic protein-1 in the endometrium of women with endometriosis. Am J Pathol 152:125–133

    CAS  PubMed  Google Scholar 

  16. Kokorine I, Marbaix E, Henriet P et al (1996) Focal cellular origin and regulation of interstitial collagenase (matrix metalloproteinase-1) are related to menstrual breakdown in the human endometrium. J Cell Sci 109:2151–2160

    CAS  PubMed  Google Scholar 

  17. Kokorine I, Nisolle M, Donnez J, Eeckhout Y, Courtoy PJ, Marbaix E (1997) Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions. Fertil Steril 68:246–251

    Article  CAS  PubMed  Google Scholar 

  18. Liokumovich P, Goldberg I, Davidson B, Gotlieb WH, Zahavi T, Ben Baruch G (1999) Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis. J Clin Pathol 52:198–202

    CAS  PubMed  Google Scholar 

  19. Mizumoto H, Saito T, Ashihara K et al (2002) Expression of matrix metalloproteinases in ovarian endometriomas: immunohistochemical study and enzyme immunoassay. Life Sci 71:259–273

    Article  CAS  PubMed  Google Scholar 

  20. Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274:21491–2149

    Article  CAS  PubMed  Google Scholar 

  21. Noble LS, Simpson ER, Johns A, Bulun SE (1996) Aromatase expression in endometriosis. J Clin Endocrinol Metab 81:174–179

    Article  CAS  PubMed  Google Scholar 

  22. Osteen KG, Keller NR, Feltus FA, Melner MH (1999) Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium. Gynecol Obstet Invest 48[Suppl 1]:2–13

    Google Scholar 

  23. Osteen KG, Igarashi TM, Bruner-Tran KL (2003) Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci 8:78–86

    Google Scholar 

  24. Osteen KG, Yeaman GR, Bruner-Tran KL (2003) Matrix metalloproteinases and endometriosis. Semin Reprod Med 21:155–164

    Article  CAS  PubMed  Google Scholar 

  25. Poncelet C, Leblanc M, Walker-Combrouze F et al (2002) Expression of cadherins and CD44 isoforms in human endometrium and peritoneal endometriosis. Acta Obstet Gynecol Scand 81:195–203

    Article  PubMed  Google Scholar 

  26. Ria R, Loverro G, Vacca A et al (2002) Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 agree with progression of ovarian endometriomas. Eur J Clin Invest 32:199–206

    Article  CAS  PubMed  Google Scholar 

  27. Ridley JH (1981) Coelomic metaplasia. Am J Obstet Gynecol 140:233–234

    CAS  PubMed  Google Scholar 

  28. Ryan IP, Taylor RN (1997) Endometriosis and infertility: new concepts. Obstet Gynecol Surv 52:365–371

    Article  CAS  PubMed  Google Scholar 

  29. Sampson JA (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469

    Google Scholar 

  30. Sillem M, Prifti S, Koch A, Neher M, Jauckus J, Runnebaum B (2001) Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis. Eur J Obstet Gynecol Reprod Biol 95:167–174

    Article  CAS  PubMed  Google Scholar 

  31. Stovall DW, Bowser LM, Archer DF, Guzick DS (1997) Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain. Fertil Steril 68:13–18

    Article  CAS  PubMed  Google Scholar 

  32. Ueda M, Yamashita Y, Takehara M et al (2002) Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis. Gynecol Endocrinol 16:391–402

    CAS  PubMed  Google Scholar 

  33. Vercellini P, Trespidi L, De Giorgi O, Cortesi I, Parazzini F, Crosignani PG (1996) Endometriosis and pelvic pain: relation to disease stage and localization. Fertil Steril 65:299–304

    CAS  PubMed  Google Scholar 

  34. Wenzl RJ, Heinzl H (1998) Localization of matrix metalloproteinase-2 in uterine endometrium and ectopic implants. Gynecol Obstet Invest 45:253–257

    Article  CAS  PubMed  Google Scholar 

  35. Wingfield M, Macpherson A, Healy DL, Rogers PA (1995) Cell proliferation is increased in the endometrium of women with endometriosis. Fertil Steril 64:340–346

    CAS  PubMed  Google Scholar 

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Acknowledgement

We want to thank the “Ligue contre le cancer” for the grant.

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Authors and Affiliations

  1. Service d’Anatomie Pathologie, Hôpital Tenon, AP-HP, France

    Catherine Uzan & Annie Cortez

  2. UPRESS EA 1533 UFR Saint-Antoine, Université Paris VI, Paris, France

    Catherine Uzan

  3. Service de Gynécologie, Hôpital Tenon, 4 rue de la Chine, 75020 , Paris, France

    Charlotte Dufournet, Raffaèle Fauvet & Emile Daraï

  4. Laboratoire de cytogénétique, Hôpital Tenon, AP-HP, France

    Jean-Pierre Siffroi

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  1. Catherine Uzan
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  2. Annie Cortez
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  3. Charlotte Dufournet
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  4. Raffaèle Fauvet
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  5. Jean-Pierre Siffroi
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  6. Emile Daraï
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Correspondence to Emile Daraï.

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Uzan, C., Cortez, A., Dufournet, C. et al. Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases-2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2. Virchows Arch 445, 603–609 (2004). https://doi.org/10.1007/s00428-004-1117-y

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  • DOI: https://doi.org/10.1007/s00428-004-1117-y

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