Skip to main content

Advertisement

SpringerLink
Log in

Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland

  • Research Article
  • Published:
Tumor Biology

Abstract

The aim of this study was to determine the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitors of matrix metalloproteinase 2 (TIMP-2) and the MMP-2/TIMP-2 expression ratio in salivary gland tumours (SGTs). Forty-three FFPE SGTs were prepared for antibody processing to MMP-2 and TIMP-2. Two investigators utilizing Sinicrope’s method scored the uptake of immuno-stains. Cytoplasmic staining was considered as positive. Data was analysed using SPSS version 20. The significance level was set at p < 0.05. In benign SGTs, the mean score for MMP-2 was not significantly lower than that of TIMP-2 (p = 0.37). However, the mean scores for MMP-2 stain intensity and proportion were significantly higher in malignant than benign SGTs (p = 0.01 and p = 0.02 respectively). There was no significant difference in the mean MMP-2/TIMP-2 expression ratio of the malignant SGTs according to histological grade and histogenesis (p = 0.4 and p = 0.19 respectively). The MMP-2/TIMP-2 expression ratio has a higher prognostic value than the separate expressions of MMP-2 and TIMP-2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci. 2000;57:5–15.

    Article  CAS  PubMed  Google Scholar 

  2. Mook ORF, Frederiks WM, Van Noorden CJF. The role of gelatinases in colorectal cancer progression and metastasis. Biochem Biophys Acta. 2004;1705:69–89.

    CAS  PubMed  Google Scholar 

  3. Hayakawa T, Yamashita K, Ohuchi E, Shinagawa A. Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2). J Cell Sci. 1994;107:2373–9.

    CAS  PubMed  Google Scholar 

  4. Stettler-Stevenson WG, Krutzsch HC, Liotta LA. TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family. Matrix Suppl. 1992;1:299–306.

    Google Scholar 

  5. Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997;74:111–22.

    CAS  PubMed  Google Scholar 

  6. Zhang X, Wang Y, Tamamoto G, Tachikawa T. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in the epithelium and stroma of salivary gland pleomorphic adenomas. Histopathology. 2009;55(3):250–60.

    Article  PubMed  Google Scholar 

  7. Kayano K, Shimada T, Shinomiya T, Nakai S, Hisa Y, Aoki T, et al. Activation of pro-MMP-2 mediated by MT1-MMP in human salivary gland carcinomas: possible regulation of pro-MMP-2 activation by TIMP-2. J Pathol. 2004;202(4):403–11.

    Article  CAS  PubMed  Google Scholar 

  8. Nagel H, Laskawi R, Wahlers A, Hemmerlein B. Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1, -2, and -3 in benign and malignant tumours of the salivary gland. Histopathology. 2004;44(3):222–31.

    Article  CAS  PubMed  Google Scholar 

  9. Batsakis JG, Luna MA. Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. Ann Otol Rhinol Laryngol. 1990;99:835–8.

    Article  CAS  PubMed  Google Scholar 

  10. Seifert G, Sobin LH. The World Health Organization’s histological classification of salivary gland tumors. A commentary on the second edition. Cancer. 1992;70(2):379–85.

    Article  CAS  PubMed  Google Scholar 

  11. Sinicrope FA, Ruan SB, Cleary KR, et al. bcl-2 and p53 onco-protein expression during colorectal tumorigenesis. Cancer Res. 1995;55:237–41.

    CAS  PubMed  Google Scholar 

  12. AL-Rawi NH, Al-Samarai M, Al-Kawas S, Majeed AH. Expression of matrix metalloproteinase MMP-2 and its tissue inhibitor TIMP-2 in intraoral pleomorphic adenoma and adenoid cystic carcinoma. J Int Dent Med Res. 2011;4:1–6.

    Google Scholar 

  13. Matrisian L. The matrix degrading metalloproteinases. Bioassays. 1992;14:455–9.

    Article  CAS  Google Scholar 

  14. Kinoshita T, Sato H, Okada A, et al. TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads. J Biol Chem. 1998;273:16098–103.

    Article  CAS  PubMed  Google Scholar 

  15. Butler GS, Butler MJ, Atkinson SJ, et al. The TIMP-2 membrane type 1 metalloproteinase ‘receptor’ regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem. 1998;273:871–80.

    Article  CAS  PubMed  Google Scholar 

  16. Onisto M, Riccio MP, Scannapieco P, et al. Gelatinase A/TIMP-2 imbalance in lymph-node-positive breast carcinomas, as measured by RT-PCR. Int J Cancer. 1995;63:621–6.

    Article  CAS  PubMed  Google Scholar 

  17. Taher MG, Abdullah BH, Al-Kari LE. Expression of MMP-2 as biological markers of invasion potential in mucoepidermoid carcinoma of the oral and maxillofacial region (immunohistochemical study). Diyala J Med. 2012;3:67–72.

    Google Scholar 

  18. Sierl CFM, Kubben FJGM, Ganeshl S, Heerding MM, Griffioen G, Hanemaaijer R, et al. Lamers’ CBHW and Verspaget’ HW. Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer. 1996;74:413–7.

    Article  Google Scholar 

  19. Yoshizaki T, Maruyama Y, Sato H, Furukawa M. Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma. Int J Cancer. 2001;95:44–50.

    Article  CAS  PubMed  Google Scholar 

  20. Kanayama H, Yokota K, Kurokawa Y, Murakami Y, Nishitani S, Kagawa S. Prognostic value of matrix metalloproteinase-2 expression and tissue inhibitor of metalloproteinase-2 expression in bladder cancer. Cancer. 1998;82:1359–66.

    Article  CAS  PubMed  Google Scholar 

  21. Jinga DC, Blidaru A, Condrea I, et al. MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors. J Cell Mol Med. 2006;10:499–510.

    Article  CAS  PubMed  Google Scholar 

  22. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387.

    Article  CAS  PubMed  Google Scholar 

  23. Chaudhary AK, Singh M, Bharti AC, Asotra K, Sundaram S, Mehrotra R. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck. J Biomedical Sci. 2010;17(10):1–13.

    Google Scholar 

Download references

Financial support

All the authors declare that there are no disclosures to make and that this was a self-funded study.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Oral Pathology, Faculty of Dentistry, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria

    Bamidele Kolude, Akinyele Olumuyiwa Adisa, Ahmed Oluwatoyin Lawal, Bukola Folasade Adeyemi & Akindayo Olufunto Akinyamoju

Authors
  1. Bamidele Kolude
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akinyele Olumuyiwa Adisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed Oluwatoyin Lawal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bukola Folasade Adeyemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akindayo Olufunto Akinyamoju
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akinyele Olumuyiwa Adisa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kolude, B., Adisa, A.O., Lawal, A.O. et al. Stoichiometric expression of MMP-2/TIMP-2 in benign and malignant tumours of the salivary gland. Tumor Biol. 36, 2351–2357 (2015). https://doi.org/10.1007/s13277-014-2842-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2842-8

Keywords

Search

Navigation