Skip to main content

Advertisement

SpringerLink
Log in

Expression and correlation of matrix metalloproteinase-9 and heparanase in patients with breast cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Matrix metalloproteinase-9 (MMP-9) and heparanase (HPSE) are thought to be involved in tumor progression and metastasis. However, up to now, there are no studies that simultaneously investigated the expression levels of MMP-9 and HPSE in tumor tissue and serum of breast cancer patients. Their correlation in breast cancer pathological processes is unknown. The purpose of this study was to investigate the expression profile of MMP-9 and HPSE in breast cancer and to assess their clinicopathological significance. We measured serum MMP-9 and HPSE by enzyme-linked immunosorbent assay in healthy women, and in patients with benign and malignant breast disease. We also evaluated the expression of MMP-9 and HPSE protein in paraffin-embedded tumor tissues by immunohistochemistry. We then correlated serum and tissue levels of MMP-9 and HPSE in breast cancer samples and their expression with patients’ clinicopathologic characteristics. We found that serum levels of MMP-9 and HPSE were significantly higher in breast cancer patients than in benign breast disease and in healthy controls (P = 0.001). There was positive correlation between MMP-9 and HPSE in breast cancer patients. The tissue and serum levels of MMP-9 were associated with histology grade, lymph node status, pathological stage, and lymphovascular invasion (all P < 0.05). The tissue levels of MMP-9 were also associated with ER (P = 0.038) and Ki-67 (P = 0.032). The tissue and serum levels of HPSE expression were associated with tumor size, histology grade, lymph node status, and pathological stage (all P < 0.05). Our findings suggested that MMP-9 and HPSE might further be evaluated as biomarkers for predicting progression and prognosis of breast cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Veronesi U, Marubini E, Del Vecchio M, et al. Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events. J Natl Cancer Inst. 1995;87:19–27.

    Article  CAS  PubMed  Google Scholar 

  3. Liotta LA, Tryggvason K, Garbisa S, et al. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980;284:67–8.

    Article  CAS  PubMed  Google Scholar 

  4. Reiland J, Sanderson RD, Waguespack M, et al. Heparanase degrades syndecan-1 and perlecan heparan sulfate functional implications for tumor cell invasion. J Biol Chem. 2004;279:8047–55.

    Article  CAS  PubMed  Google Scholar 

  5. Gomes AM, Stelling MP, Pavão MSG. Heparan sulfate and heparanase as modulators of breast cancer progression. BioMed Res Int. 2013;2013:852093.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Cupić DF, Tesar EC, Ilijas KM, et al. Expression of matrix metalloproteinase 9 in primary and recurrent breast carcinomas. Coll Antropol. 2011;35:7–10.

    PubMed  Google Scholar 

  7. Wu ZS, Wu Q, Yang JH, et al. Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer. 2008;122:2050–6.

    Article  CAS  PubMed  Google Scholar 

  8. Jones JL, Glynn P, Walker RA. Expression of MMP-2 and MMP-9, their inhibitors, and the activator MT1-MMP in primary breast carcinomas. J Pathol. 1999;189:161–8.

    Article  CAS  PubMed  Google Scholar 

  9. Nanda DP, Sil H, Moulik S, et al. Matrix metalloproteinase-9 as a potential tumor marker in breast cancer. J Environ Pathol Toxicol Oncol. 2013;32:115–29.

    Article  CAS  PubMed  Google Scholar 

  10. Zhao M, Hu HG, Huang J, et al. Expression and correlation of Twist and gelatinases in breast cancer. Exp Ther Med. 2013;6:97–100.

    PubMed Central  PubMed  Google Scholar 

  11. Maxhimer JB, Quiros RM, Stewart R, et al. Heparanase-1 expression is associated with the metastatic potential of breast cancer. Surgery. 2002;132:326–33.

    Article  PubMed  Google Scholar 

  12. Tang D, Zhang Q, Zhao S, et al. The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer. Clin Biochem. 2013;46:926–32.

    Article  CAS  PubMed  Google Scholar 

  13. Zhao S, Ma W, Zhang M, et al. High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients. Med Oncol. 2013;30:335.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Sung H, Choi JY, Lee SA, et al. The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer. BMC Cancer. 2012;12:193.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Patel S, Sumitra G, Koner BC, Saxena A. Role of serum matrix metalloproteinase-2 and -9 to predict breast cancer progression. Clin Biochem. 2011;44:869–72.

    Article  CAS  PubMed  Google Scholar 

  16. La Rocca G, Pucci-Minafra I, Marrazzo A, et al. Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. Br J Cancer. 2004;90:1414–21.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Zhang W, Yang HC, Wang Q, et al. Clinical value of combined detection of serum matrix metalloproteinase-9, heparanase, and cathepsin for determining ovarian cancer invasion and metastasis. Anticancer Res. 2011;31:3423–8.

    CAS  PubMed  Google Scholar 

  18. Rao JS, Gondi C, Chetty C, et al. Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non–small cell lung cancer cells. Mol Cancer Ther. 2005;4:1399–408.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Cassinelli G, Lanzi C, Tortoreto M, et al. Antitumor efficacy of the heparanase inhibitor SST0001 alone and in combination with antiangiogenic agents in the treatment of human pediatric sarcoma models. Biochem Pharmacol. 2013;85:1424–32.

    Article  CAS  PubMed  Google Scholar 

  20. Chen Y, Chen Y, Huang L, et al. Evaluation of heparanase and matrix metalloproteinase-9 in patients with cutaneous malignant melanoma. J Dermatol. 2012;39:339–43.

    Article  CAS  PubMed  Google Scholar 

  21. Raghu H, Sodadasu PK, Malla RR, et al. Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells. BMC Cancer. 2010;10:647.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Fux L, Feibish N, Cohen-Kaplan V, et al. Structure-function approach identifies a COOH-terminal domain that mediates heparanase signaling. Cancer Res. 2009;69:1758–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Doweck I, Kaplan-Cohen V, Naroditsky I, et al. Heparanase localization and expression by head and neck cancer: correlation with tumor progression and patient survival. Neoplasia (New York, NY). 2006;8:1055.

    Article  CAS  Google Scholar 

  24. Purushothaman A, Chen L, Yang Y, et al. Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. J Biol Chem. 2008;283:32628–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by the foundation of science and technology research project of Heilongjiang education department.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The Tumor Hospital of Harbin Medical University, Harbin, 150040, China

    Dabei Tang, Ying Piao, Shu Zhao, Xudong Mu, Shuo Li, Wenjie Ma, Ying Song, Jingxuan Wang, Wenhui Zhao & Qingyuan Zhang

  2. Oncobiology Key Lab of Heilongjiang Common Institution of Higher Learning, Harbin, 150040, China

    Qingyuan Zhang

Authors
  1. Dabei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Piao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xudong Mu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjie Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ying Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jingxuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wenhui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qingyuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wenhui Zhao or Qingyuan Zhang.

Additional information

Dabei Tang and Ying Piao are the first authors.

Wenhui Zhao and Qingyuan Zhang have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, D., Piao, Y., Zhao, S. et al. Expression and correlation of matrix metalloproteinase-9 and heparanase in patients with breast cancer. Med Oncol 31, 26 (2014). https://doi.org/10.1007/s12032-014-0026-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0026-4

Keywords

Search

Navigation