Skip to main content

Advertisement

SpringerLink
Log in

High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients

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

Abstract

The aim of this study was to investigate expression of CD147 and MMP-9 in triple-negative breast cancer (TNBC) so as to determine whether these two proteins may be correlated with poor prognosis of TNBC patients. We examined the expression levels of the CD147 and MMP-9 in 127 patients with TNBC and 30 patients with mammary gland fibroma using immunohistochemical staining before any treatments. Furthermore, we analyzed the correlation between the expression of these two proteins and various clinicopathologic factors including survival status of patients with TNBC. Positive stain of CD147 and MMP-9 was observed in all samples of TNBC. A statistically positive correlation was observed between the expression levels of CD147 and MMP-9 in TNBC tissues. The incidences of high expression were 48.0 % for CD147 and 53.5 % for MMP-9 in 127 TNBC tissues, respectively. High expression of either CD147 or MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (PCD147 = 0.039; PMMP-9 = 0.017) and overall survival (OS) (PCD147 = 0.037; PMMP-9 = 0.023). The expression levels of CD147 and MMP-9 are positively correlated with invasion, metastasis and shorter PFS/OS of TNBC. Patients with high expression of CD147 and MMP-9 had poor prognosis than TNBC patients with low expression.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumors. Nature. 2000;406:747–52.

    Article  PubMed  CAS  Google Scholar 

  2. Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res. 2007;9:R65.

    Article  PubMed  Google Scholar 

  3. Reis-Filho JS, Tutt AN. Triple negative tumors: a critical review. Histopathology. 2008;52:108–18.

    Article  PubMed  CAS  Google Scholar 

  4. Kang SP, Martel M, Harris LN. Triple negative breast cancer: current understanding of biology and treatment options. Curr Opin Obstet Gynecol. 2008;20:40–6.

    Article  PubMed  Google Scholar 

  5. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.

    Article  PubMed  Google Scholar 

  6. Tang Yi, Nakada Marian T, Kesavan Prabakaran, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 2005;65:3193–9.

    PubMed  CAS  Google Scholar 

  7. Toole BP. Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function. Curr Top Dev Biol. 2003;54:371–89.

    Article  PubMed  CAS  Google Scholar 

  8. Zheng HC, Takahashi H, Murai Y, et al. Upregulated EMM-PRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 2006;95:1371–8.

    Article  PubMed  CAS  Google Scholar 

  9. Li Z, Ren Y, Wu QC, et al. Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and inter-leukin-8 in nasopharyngeal carcinoma cell lines. Chin Med J. 2004;117:107–14.

    PubMed  CAS  Google Scholar 

  10. HymowitzM Zucker, Rollo EE, et al. Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol. 2001;158:1921–8.

    Article  Google Scholar 

  11. Mira E, Lacalle RA, Buesa JM, et al. Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface. J Cell Sci. 2004;117:1847–57.

    Article  PubMed  CAS  Google Scholar 

  12. Yu WW, Liu JH, Xiong XL, et al. Expression of MMP-9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract. 2009;205:709–15.

    Article  PubMed  CAS  Google Scholar 

  13. Tang J, Zhou HW, Jiang JL, et al. ßig-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells. Exp Biol Med. 2007;232:344–52.

    CAS  Google Scholar 

  14. Davidson B, Goldberg I, Berner A, et al. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis. 2003;20:161–9.

    Article  PubMed  CAS  Google Scholar 

  15. Ramos-DeSimone N, Hahn-Dantona E, Sipley J, et al. Activation of matrix metalloprotease-9 (MMP-9) via converting plasmin/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem. 1999;274:13066–76.

    Article  PubMed  CAS  Google Scholar 

  16. Alizadeh AA, Ross DT, Perou CM, Ven de Rijn M. Towards a novel classification of human malignancies based on gene expression patterns. J Pathol. 2010;195:41–52.

    Article  Google Scholar 

  17. Kashiwagi S, et al. Significance of E-cadherin expression in triple-negative breast cancer. Br J Cancer. 2010;103:249–55.

    Article  PubMed  CAS  Google Scholar 

  18. Liu Z, Li L, Yang ZX, et al. Research article Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. 2010;10:270–5.

    Article  PubMed  Google Scholar 

  19. Wang S, Zhou J, Wang XY, et al. Down-regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer. J Pathol. 2009;219:114–22.

    Article  PubMed  CAS  Google Scholar 

  20. Masunaga R, Kohno H, Dhar DK, et al. Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res. 2000;6:4064–8.

    PubMed  CAS  Google Scholar 

  21. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  22. Li Y, Shang P, Qian AR, et al. Inhibitory effects of antisense RNA of HAb18G/CD147 on invasion of hepatocellular carcinoma cells in vitro. World J Gastroenterol. 2003;9:2174–7.

    PubMed  CAS  Google Scholar 

  23. Reimers N, Za frakas K, Assmann V, et al. Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells. Clin Cancer Res. 2004;10:3422–8.

    Article  PubMed  CAS  Google Scholar 

  24. Chakraborti S, Mandal M, Das S, et al. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003;253:269–85.

    Article  PubMed  CAS  Google Scholar 

  25. Opdenakker G, Van den Steen PE, Van Damme J, Gelatinase B. A tuner and amplifier of immune functions. Trends Immunol. 2001;22:571–9.

    Article  PubMed  CAS  Google Scholar 

  26. Opdenakker G, Van den Steen PE, Dubois B, et al. Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol. 2001;69:851–9.

    PubMed  CAS  Google Scholar 

  27. Matache C, Stefanescu M, Dragomir C, et al. Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun. 2003;20:323–31.

    Article  PubMed  CAS  Google Scholar 

  28. Li Y, Jing X, Li C, et al. HAb18G (CD147), a cancer-associated biomarker and its role in cancer detection. Histopathology. 2009;54:677–87.

    Article  PubMed  CAS  Google Scholar 

  29. Piao S, Zhao S, Guo F, et al. Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol. 2012;138:627–35.

    Article  PubMed  CAS  Google Scholar 

  30. Ju XZ, Yang JM, Zhou XY, et al. EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer. Clin Cancer Res. 2008;14:494–501.

    Article  PubMed  CAS  Google Scholar 

  31. Chen X, Lin J, Kanekura T, et al. A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res. 2006;66:11323–30.

    Article  PubMed  CAS  Google Scholar 

  32. Rao JS, Ra C, Gondi 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  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This experiment was finished in the Oncobiology Key Lab of the Heilongjiang Province Common Institution of Higher Learning. This work was supported by the National Natural Science Foundation of China [grant number 81071889] and Harbin science and technology innovation young talents research funds [grant number 2007RFQXS086].

Conflict of interest

All authors declared that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin, 150081, Heilongjiang Province, China

    Shu Zhao, Wenjie Ma, Minghui Zhang, Dabei Tang, Shanqi Xu, Xiaosan Zhang, Ying Song & Qingyuan Zhang

  2. Department of Pathology, The Third Affiliated Hospital of Harbin Medical University, Harbin, 150081, China

    Qingtao Shi

  3. Department of Epidemiology, Public Health College of Harbin Medical University, Harbin, 150040, China

    Yupeng Liu

  4. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, 77030, USA

    Leyuan Liu

Authors
  1. Shu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenjie Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minghui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dabei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qingtao Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shanqi Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaosan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yupeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ying Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Leyuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qingyuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingyuan Zhang.

Additional information

Shu Zhao and Wenjie Ma contributed equally to the work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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 30, 335 (2013). https://doi.org/10.1007/s12032-012-0335-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-012-0335-4

Keywords

Search

Navigation