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Published in: Reproductive Biology and Endocrinology 1/2015

Open Access 01-12-2015 | Research

The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis

Authors: Mei Yang, Chunfan Jiang, Hua Chen, Yan Nian, Zhimiao Bai, Chunfang Ha

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

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Abstract

Background

Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration.

Methods

We performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs.

Results

The expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment.

Conclusions

The present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.
Literature
1.
go back to reference Vercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261–75.CrossRefPubMed Vercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261–75.CrossRefPubMed
2.
go back to reference Starzinski-Powitz A, Zeitvogel A, Schreiner A, Baumann R. In search of pathogenic mechanisms in endometriosis: the challenge for molecular cell biology. Curr Mol Med. 2001;1:655–64.CrossRefPubMed Starzinski-Powitz A, Zeitvogel A, Schreiner A, Baumann R. In search of pathogenic mechanisms in endometriosis: the challenge for molecular cell biology. Curr Mol Med. 2001;1:655–64.CrossRefPubMed
3.
4.
go back to reference Anborgh PH, Mutrie JC, Tuck AB, Chambers AF. Role of the metastasis-promoting protein osteopontin in the tumour microenvironment. J Cell Mol Med. 2010;14:2037–44.PubMedCentralCrossRefPubMed Anborgh PH, Mutrie JC, Tuck AB, Chambers AF. Role of the metastasis-promoting protein osteopontin in the tumour microenvironment. J Cell Mol Med. 2010;14:2037–44.PubMedCentralCrossRefPubMed
5.
go back to reference Song G, Cai QF, Mao YB, Mao YB, Ming YL, Bao SD, et al. Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway. Cancer Sci. 2008;99:1901–7.PubMed Song G, Cai QF, Mao YB, Mao YB, Ming YL, Bao SD, et al. Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway. Cancer Sci. 2008;99:1901–7.PubMed
6.
go back to reference Liu J, Liu Q, Wan Y, Zhao Z, Yu H, Luo H, et al. Osteopontin promotes the progression of gastric cancer through the NF-kappaB pathway regulated by the MAPK and PI3K. Int J Oncol. 2014;45:282–90.PubMed Liu J, Liu Q, Wan Y, Zhao Z, Yu H, Luo H, et al. Osteopontin promotes the progression of gastric cancer through the NF-kappaB pathway regulated by the MAPK and PI3K. Int J Oncol. 2014;45:282–90.PubMed
7.
go back to reference von Wolff M, Strowitzki T, Becker V, Zepf C, Tabibzadeh S, Thaler CJ. Endometrial osteopontin, a ligand of beta3-integrin, is maximally expressed around the time of the “implantation window”. Fertil Steril. 2001;76:775–81.CrossRef von Wolff M, Strowitzki T, Becker V, Zepf C, Tabibzadeh S, Thaler CJ. Endometrial osteopontin, a ligand of beta3-integrin, is maximally expressed around the time of the “implantation window”. Fertil Steril. 2001;76:775–81.CrossRef
8.
go back to reference Allan G, Campen C, Hodgen G, Williams R, Charnock-Jones DS, Wan J, et al. Identification of genes with differential regulation in primate endometrium during the proliferative and secretory phases of the cycle. Endocr Res. 2003;29:53–65.CrossRefPubMed Allan G, Campen C, Hodgen G, Williams R, Charnock-Jones DS, Wan J, et al. Identification of genes with differential regulation in primate endometrium during the proliferative and secretory phases of the cycle. Endocr Res. 2003;29:53–65.CrossRefPubMed
9.
go back to reference Curry Jr TE, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev. 2003;24:428–65.CrossRefPubMed Curry Jr TE, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev. 2003;24:428–65.CrossRefPubMed
10.
go back to reference Skinner JL, Riley SC, Gebbie AE, Glasier AF, Critchley HO. Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel. Hum Reprod. 1999;14:793–9.CrossRefPubMed Skinner JL, Riley SC, Gebbie AE, Glasier AF, Critchley HO. Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel. Hum Reprod. 1999;14:793–9.CrossRefPubMed
11.
go back to reference Cho S, Choi YS, Seo SK, Nam A, Kim HY, Kim JH, et al. Endometrial osteopontin mRNA expression and plasma osteopontin levels are increased in patients with endometriosis. Am J Reprod Immunol. 2009;61:286–93.CrossRefPubMed Cho S, Choi YS, Seo SK, Nam A, Kim HY, Kim JH, et al. Endometrial osteopontin mRNA expression and plasma osteopontin levels are increased in patients with endometriosis. Am J Reprod Immunol. 2009;61:286–93.CrossRefPubMed
12.
go back to reference Hapangama DK, Raju RS, Valentijn AJ, Barraclough D, Hart A, Turner MA, et al. Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis. Hum Reprod. 2012;27:394–407.CrossRefPubMed Hapangama DK, Raju RS, Valentijn AJ, Barraclough D, Hart A, Turner MA, et al. Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis. Hum Reprod. 2012;27:394–407.CrossRefPubMed
13.
go back to reference Han YJ, Yoon JK, Yi SY, Moon HS, Ahn JJ, Kim HL, et al. Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis. Fertil Steril. 2009;91:2324–30.CrossRefPubMed Han YJ, Yoon JK, Yi SY, Moon HS, Ahn JJ, Kim HL, et al. Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis. Fertil Steril. 2009;91:2324–30.CrossRefPubMed
14.
go back to reference Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, et al. Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis. Gynecol Endocrinol. 2002;16:391–402.CrossRefPubMed Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, et al. Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis. Gynecol Endocrinol. 2002;16:391–402.CrossRefPubMed
15.
16.
go back to reference Huhtinen K, Desai R, Stahle M, Salminen A, Handelsman DJ, Perheentupa A, et al. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab. 2012;97:4228–35.PubMedCentralCrossRefPubMed Huhtinen K, Desai R, Stahle M, Salminen A, Handelsman DJ, Perheentupa A, et al. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab. 2012;97:4228–35.PubMedCentralCrossRefPubMed
18.
go back to reference Waller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril. 1993;59:511–5.PubMed Waller KG, Shaw RW. Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril. 1993;59:511–5.PubMed
19.
go back to reference Meresman GF, Bilotas M, Buquet RA, Barañao RI, Sueldo C, Tesone M. Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis. Fertil Steril. 2003;80:702–7.CrossRefPubMed Meresman GF, Bilotas M, Buquet RA, Barañao RI, Sueldo C, Tesone M. Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis. Fertil Steril. 2003;80:702–7.CrossRefPubMed
20.
go back to reference Meresman GF, Bilotas M, Abello V, Buquet R, Tesone M, Sueldo C. Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. Fertil Steril. 2005;84:459–63.CrossRefPubMed Meresman GF, Bilotas M, Abello V, Buquet R, Tesone M, Sueldo C. Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. Fertil Steril. 2005;84:459–63.CrossRefPubMed
21.
go back to reference Boccellino M, Quagliuolo L, Verde A, La Porta R, Crispi S, Piccolo MT, et al. In vitro model of stromal and epithelial immortalized endometriotic cells. J Cell Biochem. 2012;113:1292–301.CrossRefPubMed Boccellino M, Quagliuolo L, Verde A, La Porta R, Crispi S, Piccolo MT, et al. In vitro model of stromal and epithelial immortalized endometriotic cells. J Cell Biochem. 2012;113:1292–301.CrossRefPubMed
22.
go back to reference Hombach-Klonisch S, Kehlen A, Fowler PA, Huppertz B, Jugert JF, Bischoff G, et al. Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells. J Mol Endocrinol. 2005;34:517–34.CrossRefPubMed Hombach-Klonisch S, Kehlen A, Fowler PA, Huppertz B, Jugert JF, Bischoff G, et al. Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells. J Mol Endocrinol. 2005;34:517–34.CrossRefPubMed
23.
go back to reference Fujiwara A, Shibata E, Terashima H, Shishido A, Nishiki J, Yoshida K, et al. Evaluation of matrix metalloproteinase-2 (MMP-2) activity with film in situ zymography for improved cytological diagnosis of breast tumors. Breast Cancer. 2006;13:272–8.CrossRefPubMed Fujiwara A, Shibata E, Terashima H, Shishido A, Nishiki J, Yoshida K, et al. Evaluation of matrix metalloproteinase-2 (MMP-2) activity with film in situ zymography for improved cytological diagnosis of breast tumors. Breast Cancer. 2006;13:272–8.CrossRefPubMed
24.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMed
25.
go back to reference Chen QH, Zhou W, Pu DM, Huang QS, Li T, Chen QX. 15-Epi-lipoxin A(4) inhibits the progression of endometriosis in a murine model. Fertil Steril. 2010;95:1440–7.CrossRef Chen QH, Zhou W, Pu DM, Huang QS, Li T, Chen QX. 15-Epi-lipoxin A(4) inhibits the progression of endometriosis in a murine model. Fertil Steril. 2010;95:1440–7.CrossRef
26.
go back to reference Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–9.CrossRefPubMed Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–9.CrossRefPubMed
27.
go back to reference Witz CA, Thomas M, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001;75:385–90.CrossRefPubMed Witz CA, Thomas M, Montoya-Rodriguez IA, Nair AS, Centonze VE, Schenken RS. Short-term culture of peritoneum explants confirms attachment of endometrium to intact peritoneal mesothelium. Fertil Steril. 2001;75:385–90.CrossRefPubMed
28.
go back to reference Li MQ, Hou X, Lv S, Meng YH, Wang XQ, Wang X, et al. CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu. J Mol Endocrinol. 2011;47:195–208.CrossRefPubMed Li MQ, Hou X, Lv S, Meng YH, Wang XQ, Wang X, et al. CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu. J Mol Endocrinol. 2011;47:195–208.CrossRefPubMed
29.
go back to reference Jin A, Chen H, Wang C, Tsang LL, Jiang X, Cai Z, et al. Elevated expression of CD147 in patients with endometriosis and its role in regulating apoptosis and migration of human endometrial cells. Fertil Steril. 2014;101:1681–7.CrossRefPubMed Jin A, Chen H, Wang C, Tsang LL, Jiang X, Cai Z, et al. Elevated expression of CD147 in patients with endometriosis and its role in regulating apoptosis and migration of human endometrial cells. Fertil Steril. 2014;101:1681–7.CrossRefPubMed
30.
31.
go back to reference Trukhacheva E, Lin Z, Reierstad S, Cheng YH, Milad M, Bulun SE. Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab. 2009;94:615–22.PubMedCentralCrossRefPubMed Trukhacheva E, Lin Z, Reierstad S, Cheng YH, Milad M, Bulun SE. Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab. 2009;94:615–22.PubMedCentralCrossRefPubMed
32.
go back to reference Yotova I, Quan P, Gaba A, Leditznig N, Pateisky P, Kurz C, et al. Raf-1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis. J Cell Mol Med. 2012;16:2127–39.PubMedCentralCrossRefPubMed Yotova I, Quan P, Gaba A, Leditznig N, Pateisky P, Kurz C, et al. Raf-1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis. J Cell Mol Med. 2012;16:2127–39.PubMedCentralCrossRefPubMed
33.
go back to reference Szamatowicz J, Laudanski P, Tomaszewska I. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: a possible role in the pathogenesis of endometriosis. Hum Reprod. 2002;17:284–8.CrossRefPubMed Szamatowicz J, Laudanski P, Tomaszewska I. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1: a possible role in the pathogenesis of endometriosis. Hum Reprod. 2002;17:284–8.CrossRefPubMed
34.
go back to reference Zhou HE, Nothnick WB. The relevancy of the matrix metalloproteinase system to the pathophysiology of endometriosis. Front Biosci. 2005;10:569–75.CrossRefPubMed Zhou HE, Nothnick WB. The relevancy of the matrix metalloproteinase system to the pathophysiology of endometriosis. Front Biosci. 2005;10:569–75.CrossRefPubMed
35.
go back to reference Lagarrigue F, Dupuis-Coronas S, Ramel D, Delsol G, Tronchere H, Payrastre B, et al. Matrix metalloproteinase-9 is upregulated in nucleophosmin-anaplastic lymphoma kinase-positive anaplastic lymphomas and activated at the cell surface by the chaperone heat shock protein 90 to promote cell invasion. Cancer Res. 2010;70:6978–87.CrossRefPubMed Lagarrigue F, Dupuis-Coronas S, Ramel D, Delsol G, Tronchere H, Payrastre B, et al. Matrix metalloproteinase-9 is upregulated in nucleophosmin-anaplastic lymphoma kinase-positive anaplastic lymphomas and activated at the cell surface by the chaperone heat shock protein 90 to promote cell invasion. Cancer Res. 2010;70:6978–87.CrossRefPubMed
36.
go back to reference Paul S, Sharma AV, Mahapatra PD, Bhattacharya P, Reiter RJ, Swarnakar S. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res. 2008;44:439–49.CrossRefPubMed Paul S, Sharma AV, Mahapatra PD, Bhattacharya P, Reiter RJ, Swarnakar S. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res. 2008;44:439–49.CrossRefPubMed
Metadata
Title
The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis
Authors
Mei Yang
Chunfan Jiang
Hua Chen
Yan Nian
Zhimiao Bai
Chunfang Ha
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-015-0090-4

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