Archives of Gynecology and Obstetrics

, Volume 286, Issue 6, pp 1537–1543 | Cite as

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

  • Xiaoxia Hu
  • Danrong Li
  • Wei Zhang
  • Jie Zhou
  • Bujian Tang
  • Li Li
Gynecologic Oncology



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.


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.


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.


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.


Ovarian cancer Matrix metalloproteinase Prognosis Invasion 



This research was supported by Grants from the Guangxi Science Foundation.

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    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 31:268–277PubMedGoogle Scholar
  2. 2.
    Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67PubMedCrossRefGoogle Scholar
  3. 3.
    Stallings-Mann M, Radisky D (2007) Matrix metalloproteinase-induced malignancy in mammary epithelial cells. Cells Tissues Organs 185:104–110PubMedCrossRefGoogle Scholar
  4. 4.
    Cruz-Munoz W, Khokha R (2008) The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci 45:291–338PubMedCrossRefGoogle Scholar
  5. 5.
    Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166PubMedCrossRefGoogle Scholar
  6. 6.
    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 16:1297–1302PubMedCrossRefGoogle Scholar
  7. 7.
    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 16:1911–1917PubMedCrossRefGoogle Scholar
  8. 8.
    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 24:1417–1420Google Scholar
  9. 9.
    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 7:2396–2404PubMedGoogle Scholar
  10. 10.
    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 33:1239–1246PubMedGoogle Scholar
  11. 11.
    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) 231:20–27Google Scholar
  12. 12.
    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 31:149–155PubMedCrossRefGoogle Scholar
  13. 13.
    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 119:1403–1411PubMedCrossRefGoogle Scholar
  14. 14.
    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 97:971–977PubMedCrossRefGoogle Scholar
  15. 15.
    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 122:2050–2056PubMedCrossRefGoogle Scholar
  16. 16.
    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 39:1948–1956PubMedCrossRefGoogle Scholar
  17. 17.
    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 27:2753–2758PubMedGoogle Scholar
  18. 18.
    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 82:291–298PubMedCrossRefGoogle Scholar
  19. 19.
    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 17:673–681PubMedGoogle Scholar
  20. 20.
    Kamat AA, Fletcher M, Gruman LM et al (2006) The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer. Clin Cancer Res 12:1707–1714PubMedCrossRefGoogle Scholar
  21. 21.
    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 149:628–631PubMedCrossRefGoogle Scholar
  22. 22.
    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 28:280–289PubMedCrossRefGoogle Scholar
  23. 23.
    Sillanpää S, Anttila M, Voutilainen K et al (2007) Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol Oncol 104:296–303PubMedCrossRefGoogle Scholar
  24. 24.
    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):1049–1057PubMedGoogle Scholar
  25. 25.
    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 114:19–31PubMedCrossRefGoogle Scholar
  26. 26.
    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 119:1792–1799PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Xiaoxia Hu
    • 1
  • Danrong Li
    • 2
  • Wei Zhang
    • 2
  • Jie Zhou
    • 2
  • Bujian Tang
    • 2
  • Li Li
    • 2
  1. 1.Department of GynecologyThe People’s Hospital of Guangxi ProvinceNanningPeople’s Republic of China
  2. 2.Department of Gynecologic Oncology, Cancer Institute and HospitalGuangxi Medical UniversityNanningPeople’s Republic of China

Personalised recommendations