Skip to main content

Advertisement

SpringerLink
Log in

Extracellular Matrix Metalloproteinase Inducer is a Negative Prognostic Factor of Pediatric Medulloblastoma

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Medulloblastoma (MB) is the most common embryonal CNS tumor of childhood. Its survival rates have significantly improved over the years due to developments in diagnostic techniques and therapeutic strategies. However, it is still an important cause of cancer-related deaths in children. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells. Therefore, the aim of this study was to investigate whether the expression patterns of EMMPRIN may predict the clinical prognosis in MB. EMMPRIN expression in a series of 56 MB with various grades and pathological types was analyzed by immunohistochemical staining on paraffin-embedded sections. Then, the correlation of EMMPRIN expression patterns with clinical-pathological features of patients and its prognostic relevance were determined. Immunohistochemistry revealed that the positive expression rate of EMMPRIN in MB (75.0%, 42/56) was significantly higher than that in normal cerebellums (6.7%, 2/30, p < 0.001). In addition, EMMPRIN expression in MB was up-regulated in higher metastatic stage (p < 0.01), aggressive histopathological type (p < 0.005), necrosis (p < 0.01), as well as with undifferentiated tumor (p < 0.01). Furthermore, over-expression of EMMPRIN correlated significantly with poor prognosis (0.01 < p < 0.05) and represented an independent prognostic marker of overall survival on multivariate analysis (p = 0.01). Our study suggests that EMMPRIN expression was associated with the progression of MB and its over-activation may be an important predictor of poor survival in this patient cohort. Therefore, EMMPRIN may be regarded both as a prognostic factor and a therapeutic target for MB.

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. Ris MD, Packer R, Goldwein J et al (2001) Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a children’s cancer group study. J Clin Oncol 19:3470–6

    PubMed  CAS  Google Scholar 

  2. Taylor RE, Bailey CC, Robinson K et al (2003) Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study. J Clin Oncol 21:1581–91

    Article  PubMed  CAS  Google Scholar 

  3. Wolden SL, Dunkel IJ, Souweidane MM et al (2003) Patterns of failure using a conformal radiation therapy tumor bed boost for medulloblastoma. J Clin Oncol 21:3079–83

    Article  PubMed  Google Scholar 

  4. Douglas JG, Barker JL, Ellenbogen RG et al (2004) Concurrent chemotherapy and reduced-dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average-risk medulloblastoma: efficacy and patterns of failure. Int J Radiat Oncol Biol Phys 58:1161–4

    Article  PubMed  Google Scholar 

  5. Gabison EE, Mourah S, Steinfels E (2005) Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas. Am J Pathol 166:209–19

    Article  PubMed  CAS  Google Scholar 

  6. TangY KP, Nakada MT, Yan L (2004) Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res 2:73–80

    Google Scholar 

  7. Tang Y, Nakada MT, Kesavan P et al (2005) Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res 65:3193–9

    PubMed  CAS  Google Scholar 

  8. Marieb EA, Zoltan-Jones A, Li R et al (2004) Emmprin promotes anchorage-independent growth in human mammary carcinoma cells by stimulating hyaluronan production. Cancer Res 64:1229–32

    Article  PubMed  CAS  Google Scholar 

  9. Yang JM, O’Neill P, Jin W et al (2006) Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to anoikis through inhibition of Bim. J Biol Chem 281:9719–27

    Article  PubMed  CAS  Google Scholar 

  10. Vignesw N, Beckers S, Waigel S et al (2006) Increased EMMPRIN (CD 147) expression during oral carcinogenesis. Exp Mol Pathol 80:147–59

    Article  Google Scholar 

  11. Dai JY, Dou KF, Wang CH et al (2009) The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells. BMC Cancer 9:337

    Article  PubMed  Google Scholar 

  12. Ishibashi Y, Matsumoto T, Niwa M et al (2004) CD147 and matrix metalloproteinase-2 protein expression as significant prognostic factors in esophageal squamous cell carcinoma. Cancer 101:1994–2000

    Article  PubMed  CAS  Google Scholar 

  13. Gershon TR, Becher OJ (2006) Medulloblastoma: therapy and biologic considerations. Curr Neurol Neurosci Rep 6:200–206

    Article  PubMed  Google Scholar 

  14. Jakacki RI (2005) Treatment strategies for high-risk medulloblastoma and supratentorial primitive neuroectodermal tumors. Review of the literature. J Neurosurg 102(Suppl 1):44–52

    PubMed  Google Scholar 

  15. Yang JM, Xu Z, Wu H (2003) Overexpression of extracellular matrixmetalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res 1:420–7

    PubMed  CAS  Google Scholar 

  16. Thorns C, FellerAC MH (2002) EMMPRIN (CD147) is expressed in Hodgkin’s lymphoma and anaplastic large cell lymphoma. An immunohistochemical study of 60 cases. Anticancer Res 22:1983–6

    PubMed  CAS  Google Scholar 

  17. Maria BL, Gupta N, Gilg AG et al (2008) Targeting hyaluronan interactions in spinal cord astrocytomas and diffuse pontine gliomas. J Child Neurol 23:1214–20

    Article  PubMed  Google Scholar 

  18. TsaiWC ChaoYC, Lee WH et al (2006) Inc reasing EMMPRIN and matriptase expression in hepatocellular carcinoma: tissue microarray analysis of immunohistochemical scores with clinicopathological parameters. Histopathology 49:388–95

    Article  CAS  Google Scholar 

  19. Reimers N, ZafrakasK AssmannV et al (2004) Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells. Clin Cancer Res 10:3422–8

    Article  PubMed  CAS  Google Scholar 

  20. Davidson B, Konstantinovsky S, Nielsen S et al (2004) ltered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression. Clin Cancer Res 10:7335–46

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. Menashi S, Serova M, Ma L et al (2003) (2003) Regulation of extracellular matrix metalloproteinase inducer matrix metalloproteinase expression by amphiregulin in transformed human breast epithelial cells. Cancer Res 63:7575–80

    PubMed  CAS  Google Scholar 

  23. Jia L, Wei W, Cao J, Xu H, Miao X, Zhang J (2009) Silencing CD147 inhibits tumor progression and increases chemosensitivity in murine lymphoid neoplasm P388D1 cells. Ann Hematol 88:753–60

    Article  PubMed  CAS  Google Scholar 

  24. Kuang YH, Chen X, Su J et al (2009) RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Lett 276:189–95

    Article  PubMed  CAS  Google Scholar 

  25. Packer RJ, Rood BR, MacDonald TJ (2003) Medulloblastoma: present concepts of stratification into risk groups. Pediatr Neurosurg 39:60–7

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of orthopaedics, Xinqiao Hospital, Chongqing, 400037, People’s Republic of China

    Tongwei Chu

  2. Department of Paediatrics, the first affiliated hospital of Shantou University, Shantou, 515063, Guangdong, People’s Republic of China

    Xiaoyang Chen

  3. Department of Hematology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China

    Jie Yu & Jianwen Xiao

  4. Respiratory Center, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China

    Zhou Fu

Authors
  1. Tongwei Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoyang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianwen Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhou Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhou Fu.

Additional information

Tongwei Chu and Xiaoyang Chen have offered the equal contribution to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, T., Chen, X., Yu, J. et al. Extracellular Matrix Metalloproteinase Inducer is a Negative Prognostic Factor of Pediatric Medulloblastoma. Pathol. Oncol. Res. 17, 705–711 (2011). https://doi.org/10.1007/s12253-011-9373-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-011-9373-z

Keywords

Search

Navigation