Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 6/2012

01.12.2012 | Gynecologic Oncology

Matrix metalloproteinase-9 expression correlates with prognosis and involved in ovarian cancer cell invasion

verfasst von: Xiaoxia Hu, Danrong Li, Wei Zhang, Jie Zhou, Bujian Tang, Li Li

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

One of the most important characteristics of ovarian cancer is invasion and metastasis. Matrix metalloproteinases (MMPs) are known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix (ECM). The activities of MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs). In this study, we investigated the clinical significance of MMP-2, -7 and -9 and TIMP-1, -2 and -3 expression and MMP-9 functional role in cell invasion and adhesion in ovarian cancer.

Methods

RT-PCR was used to determine mRNA expression of MMP-2, -7 and -9 and TIMP-1, -2 and -3 in ovarian tissues; ELISA was used to detect the serum level of MMP-9; RNA interference (RNAi) was performed to determine the function of MMP-9 in cell invasion and adhesion in ovarian cancer cells.

Results

mRNA expression of MMP-2, MMP-7, MMP-9, TIMP-2 and TIMP-3 and serum level of MMP-9 were significantly high in patients with ovarian cancer. MMP-9 expression was significantly high in patients with advanced ovarian cancer and correlated with poor prognosis. The ability of cells for invasion and adhesion was significantly reduced by treatment of cells with MMP-9 siRNA.

Conclusions

Our results suggest that MMP-9 is a potential prognostic factor for ovarian cancer and could be a novel treatment target in ovarian cancer patients.
Literatur
1.
Zurück zum Zitat Zagouri F, Dimopoulos MA, Bournakis E, Papadimitriou CA (2010) Molecular markers in epithelial ovarian cancer: their role in prognosis and therapy. Eur J Gynaecol Oncol 31:268–277PubMed Zagouri F, Dimopoulos MA, Bournakis E, Papadimitriou CA (2010) Molecular markers in epithelial ovarian cancer: their role in prognosis and therapy. Eur J Gynaecol Oncol 31:268–277PubMed
2.
Zurück zum Zitat Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67PubMedCrossRef Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67PubMedCrossRef
3.
Zurück zum Zitat Stallings-Mann M, Radisky D (2007) Matrix metalloproteinase-induced malignancy in mammary epithelial cells. Cells Tissues Organs 185:104–110PubMedCrossRef Stallings-Mann M, Radisky D (2007) Matrix metalloproteinase-induced malignancy in mammary epithelial cells. Cells Tissues Organs 185:104–110PubMedCrossRef
4.
Zurück zum Zitat Cruz-Munoz W, Khokha R (2008) The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 45:291–338PubMedCrossRef Cruz-Munoz W, Khokha R (2008) The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 45:291–338PubMedCrossRef
5.
Zurück zum Zitat Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166PubMedCrossRef Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166PubMedCrossRef
6.
Zurück zum Zitat Rauvala M, Aglund K, Puistola U, Turpeenniemi-Hujanen T, Horvath G, Willén R, Stendahl U (2006) Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression. Int J Gynecol Cancer 16:1297–1302PubMedCrossRef Rauvala M, Aglund K, Puistola U, Turpeenniemi-Hujanen T, Horvath G, Willén R, Stendahl U (2006) Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression. Int J Gynecol Cancer 16:1297–1302PubMedCrossRef
7.
Zurück zum Zitat Graesslin O, Cortez A, Uzan C, Birembaut P, Quereux C, Daraï E (2006) Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions. Int J Gynecol Cancer 16:1911–1917PubMedCrossRef Graesslin O, Cortez A, Uzan C, Birembaut P, Quereux C, Daraï E (2006) Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expressions. Int J Gynecol Cancer 16:1911–1917PubMedCrossRef
8.
Zurück zum Zitat Ozalp S, Tanir HM, Yalcin OT, Kabukcuoglu S, Oner U, Uray M (2003) Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors. Eur J Gynaecol Oncol 24:1417–1420 Ozalp S, Tanir HM, Yalcin OT, Kabukcuoglu S, Oner U, Uray M (2003) Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors. Eur J Gynaecol Oncol 24:1417–1420
9.
Zurück zum Zitat Schmalfeldt B, Prechtel D, Harting K et al (2001) Increased expression of matrix metalloproteinases (MMP)-2, MMP-9 and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin Cancer Res 7:2396–2404PubMed Schmalfeldt B, Prechtel D, Harting K et al (2001) Increased expression of matrix metalloproteinases (MMP)-2, MMP-9 and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin Cancer Res 7:2396–2404PubMed
10.
Zurück zum Zitat Brun JL, Cortez A, Commo F, Uzan S, Uzan S, Rouzier R, Daraï E (2008) Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2. Int J Oncol 33:1239–1246PubMed Brun JL, Cortez A, Commo F, Uzan S, Uzan S, Rouzier R, Daraï E (2008) Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2. Int J Oncol 33:1239–1246PubMed
11.
Zurück zum Zitat Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y (2006) Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood) 231:20–27 Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y (2006) Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med (Maywood) 231:20–27
12.
Zurück zum Zitat Koskensalo S, Mrena J, Wiksten JP, Nordling S, Kokkola A, Hagström J, Haglund C (2010) MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol 31:149–155PubMedCrossRef Koskensalo S, Mrena J, Wiksten JP, Nordling S, Kokkola A, Hagström J, Haglund C (2010) MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumour Biol 31:149–155PubMedCrossRef
13.
Zurück zum Zitat Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, Shriver CD (2006) Circulating MMP2 and MMP9 in breast cancer potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 119:1403–1411PubMedCrossRef Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, Shriver CD (2006) Circulating MMP2 and MMP9 in breast cancer potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 119:1403–1411PubMedCrossRef
14.
Zurück zum Zitat Hurst NG, Stocken DD, Wilson S, Keh C, Wakelam MJ, Ismail T (2007) Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients. Br J Cancer 97:971–977PubMedCrossRef Hurst NG, Stocken DD, Wilson S, Keh C, Wakelam MJ, Ismail T (2007) Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients. Br J Cancer 97:971–977PubMedCrossRef
15.
Zurück zum Zitat Wu ZS, Wu Q, Yang JH, Wang HQ, Ding XD, Yang F, Xu XC (2008) Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer 122:2050–2056PubMedCrossRef Wu ZS, Wu Q, Yang JH, Wang HQ, Ding XD, Yang F, Xu XC (2008) Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer 122:2050–2056PubMedCrossRef
16.
Zurück zum Zitat Manenti L, Paganoni P, Floriani I et al (2003) Expression levels of vascular endothelial growth factor, matrix metalloproteinases-2 and -9 and tissue inhibitor of metalloproteinases-1 and -2 in the plasma of patients with ovarian carcinoma. Eur J Cancer 39:1948–1956PubMedCrossRef Manenti L, Paganoni P, Floriani I et al (2003) Expression levels of vascular endothelial growth factor, matrix metalloproteinases-2 and -9 and tissue inhibitor of metalloproteinases-1 and -2 in the plasma of patients with ovarian carcinoma. Eur J Cancer 39:1948–1956PubMedCrossRef
17.
Zurück zum Zitat Määtta M, Talvensaari-Mattila A, Turpeenniemi-Hujanen T, Santala M (2007) Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours. Anticancer Res 27:2753–2758PubMed Määtta M, Talvensaari-Mattila A, Turpeenniemi-Hujanen T, Santala M (2007) Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours. Anticancer Res 27:2753–2758PubMed
18.
Zurück zum Zitat Lengyel E, Schmalfeldt B, Konik E et al (2001) Expression of latent matrix metalloproteinase-9 (MMP-9) predicts survival in advanced ovarian cancer. Gynecol Oncol 82:291–298PubMedCrossRef Lengyel E, Schmalfeldt B, Konik E et al (2001) Expression of latent matrix metalloproteinase-9 (MMP-9) predicts survival in advanced ovarian cancer. Gynecol Oncol 82:291–298PubMedCrossRef
19.
Zurück zum Zitat Sakata K, Shigemasa K, Nagai N, Ohama K (2000) Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. Int J Oncol 17:673–681PubMed Sakata K, Shigemasa K, Nagai N, Ohama K (2000) Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. Int J Oncol 17:673–681PubMed
20.
Zurück zum Zitat Kamat AA, Fletcher M, Gruman LM et al (2006) The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer. Clin Cancer Res 12:1707–1714PubMedCrossRef Kamat AA, Fletcher M, Gruman LM et al (2006) The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer. Clin Cancer Res 12:1707–1714PubMedCrossRef
21.
Zurück zum Zitat Gershtein ES, Levkina NV, Digayeva MA, Laktionov KP, Tereshkina IV, Kushlinsky NE (2010) Matrix metalloproteinases-2, -7, and -9 and tissue inhibitor of metalloproteinases-1 in tumors and serum of patients with ovarian neoplasms. Bull Exp Biol Med 149:628–631PubMedCrossRef Gershtein ES, Levkina NV, Digayeva MA, Laktionov KP, Tereshkina IV, Kushlinsky NE (2010) Matrix metalloproteinases-2, -7, and -9 and tissue inhibitor of metalloproteinases-1 in tumors and serum of patients with ovarian neoplasms. Bull Exp Biol Med 149:628–631PubMedCrossRef
22.
Zurück zum Zitat Sillanpää S, Anttila M, Suhonen K et al (2007) Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 in epithelial ovarian cancer. Tumour Biol 28:280–289PubMedCrossRef Sillanpää S, Anttila M, Suhonen K et al (2007) Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 in epithelial ovarian cancer. Tumour Biol 28:280–289PubMedCrossRef
23.
Zurück zum Zitat Sillanpää S, Anttila M, Voutilainen K et al (2007) Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol Oncol 104:296–303PubMedCrossRef Sillanpää S, Anttila M, Voutilainen K et al (2007) Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol Oncol 104:296–303PubMedCrossRef
24.
Zurück zum Zitat Brun JL, Cortez A, Lesieur B, Uzan S, Rouzier R, Daraï E (2011) Expression of MMP-2, -7, -9, MT1-MMP and TIMP-1 and -2 has no prognostic relevance in patients with advanced epithelial ovarian cancer. Oncol Rep 27(4):1049–1057PubMed Brun JL, Cortez A, Lesieur B, Uzan S, Rouzier R, Daraï E (2011) Expression of MMP-2, -7, -9, MT1-MMP and TIMP-1 and -2 has no prognostic relevance in patients with advanced epithelial ovarian cancer. Oncol Rep 27(4):1049–1057PubMed
25.
Zurück zum Zitat Wang FQ, So J, Reierstad S, Fishman DA (2005) Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase. Int J Cancer 114:19–31PubMedCrossRef Wang FQ, So J, Reierstad S, Fishman DA (2005) Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase. Int J Cancer 114:19–31PubMedCrossRef
26.
Zurück zum Zitat Sillanpää SM, Anttila MA, Voutilainen KA, Ropponen KM, Sironen RK, Saarikoski SV, Kosma VM (2006) Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian cancer and its relation to beta-catenin expression. Int J Cancer 119:1792–1799PubMedCrossRef Sillanpää SM, Anttila MA, Voutilainen KA, Ropponen KM, Sironen RK, Saarikoski SV, Kosma VM (2006) Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian cancer and its relation to beta-catenin expression. Int J Cancer 119:1792–1799PubMedCrossRef
Metadaten
Titel
Matrix metalloproteinase-9 expression correlates with prognosis and involved in ovarian cancer cell invasion
verfasst von
Xiaoxia Hu
Danrong Li
Wei Zhang
Jie Zhou
Bujian Tang
Li Li
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 6/2012
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-012-2456-6

Weitere Artikel der Ausgabe 6/2012

Archives of Gynecology and Obstetrics 6/2012 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.