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Clinical implications and prognostic value of EMMPRIN/CD147 and MMP2 expression in pediatric gliomas

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Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN), a member of the immunoglobulin superfamily, is present on the surface of tumor cells where it stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). We have analyzed the clinicopathological characteristics of EMMPRIN and MMP2 expression in normal brain tissue and pediatric gliomas and evaluated their prognostic value in diagnosing the latter. Immunochemistry analysis revealed EMMPRIN and MMP2 expression in cryo-sections of pediatric gliomas (45 samples) and normal brain tissue (20 samples). Both EMMPRIN and MMP2 were expressed in normal brain and glioma tissues with different levels of malignancy. The intensively positive expression rates of EMMPRIN (22/27) and MMP2 (21/27) in anaplastic astrocytoma and glioblastoma tissues were significantly higher than those in normal brain and low-grade astrocytoma tissues (2/28 and ½8, respectively). Spearman analysis indicated that the expression level of EMMPRIN was significantly positively correlated with that of MMP2 (r = 0.86, p < 0.01). The positive expression of EMMPRIN and MMP2 was associated with higher grade gliomas. Patients with EMMPRIN+/MMP2+ expression had the lowest survival rate (p < 0.01). Based on these results, we conclude that EMMPRIN and MMP2 are expressed differently in normal brain and pediatric gliomas. The detection of their co-expression may facilitate the prediction of pediatric gliomas prognosis.

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Abbreviations

ECM:

Extracellular matrix

EMMPRIN:

Extracellular matrix metalloproteinase inducer

MMPs:

Matrix metalloproteinases

References

  1. Brat DJ, Shehata BM, Castellano-Sanchez AA et al (2007) Congenital glioblastoma: a clinicopathologic and genetic analysis. Brain Pathol 17:276–281

    Article  PubMed  CAS  Google Scholar 

  2. Marieb EA, Zoltan-Jones A (2004) Emmprin promotes anchorage-independent growth in human mammary carcinoma cells by stimulating hyaluronan production. Cancer Res 64:1229–1232

    Article  PubMed  CAS  Google Scholar 

  3. Gabison EE, Mourah S, Steinfels E (2005) Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio- stromal interactions and matrix metalloproteinase induction. Am J Pathol 166:209–219

    PubMed  CAS  Google Scholar 

  4. Heppner KJ, Matrisian LM, Jensen RA et al (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 149:273–282

    PubMed  CAS  Google Scholar 

  5. Sun J, Hemle ME (2001) Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res 61:2276–2281

    PubMed  CAS  Google Scholar 

  6. Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3:255–268

    Article  PubMed  CAS  Google Scholar 

  7. Kossakowska AE, Huchcroft SA, Urbanski SJ et al (1996) Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin’s lymphomas in humans. Br J Cancer 73:1401–1408

    PubMed  CAS  Google Scholar 

  8. London CA, Sekhon HS, Arora V et al (2003) A novel antisense inhibitor of MMP-9 attenuates angiogenesis, human prostate cancer cell invasion and tumorigenicity. Cancer Gene Ther 10:823–832

    Article  PubMed  CAS  Google Scholar 

  9. Madigan MC, Kingsley EA, Cozzi PJ et al (2008) The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression. Cancer Immunol Immunother 57:1367–1379

    Article  PubMed  CAS  Google Scholar 

  10. Lanyi M, Antonescu CR (2002) The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147. Am J Pathol 160:1215–1221

    Google Scholar 

  11. Mi Z, Oliver T, Guo H et al (2007) Thrombin-cleaved COOH (-) terminal osteopontin peptide binds with cyclophilin C to CD147 in murine breast cancer cells. Cancer Res 67:4088–4097

    Article  PubMed  CAS  Google Scholar 

  12. Nabeshima K, Iwasaki H, Koga K et al (2006) Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int 56:359–367

    Article  PubMed  CAS  Google Scholar 

  13. Nakada M, Nakamura H, Ikeda E et al (1999) Expression and tissue localization of membrane-types 1, 2 and 3 matrix metalloproteinases in human astrocytic tumors. Am J Pathol 154:417–428

    PubMed  CAS  Google Scholar 

  14. Pulukuri SM, Patibandla S, Patel J et al (2007) Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors. Oncogene 26:5229–5237

    Article  PubMed  CAS  Google Scholar 

  15. Rainov NG, Söling A (2006) Clinical studies with targeted toxins in malignant glioma. Rev Recent Clin Trials 1:119–131

    Article  PubMed  CAS  Google Scholar 

  16. Ranuncolo SM, Armanasco E, Cresta C (2003) Plasma MMP-9 (92 kDa-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients. Int J Cancer 106:745–751

    Article  PubMed  CAS  Google Scholar 

  17. Riethdorf S, Reimers N, Assmann V (2006) High incidence of EMMPRIN expression in human tumors. Int J Cancer 119:1800–1810

    Article  PubMed  CAS  Google Scholar 

  18. Sienel W, Hellers J, Morresi-Hauf A (2003) Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer. Int J Cancer 103:647–651

    Article  PubMed  CAS  Google Scholar 

  19. Zucker S, Hymowitz M, Rollo EE (2001) Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol 158:1921–1928

    PubMed  CAS  Google Scholar 

  20. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  21. Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166

    Article  PubMed  CAS  Google Scholar 

  22. Wykosky J, Gibo DM, Stanton C et al (2005) EphA2 as a novel molecular marker and target in glioblastoma multiform. Mol Cancer Res 3:541–551

    Article  PubMed  CAS  Google Scholar 

  23. Tang Y, Nakada MT (2005) Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating ascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res 65:3193–3199

    PubMed  CAS  Google Scholar 

  24. Ishibashi Y, Matsumoto T, Niwa M (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 

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Authors and Affiliations

  1. Department of Pediatrics, Taihe Hospital Affiliated with the Yunyang Medical College, Shiyan, Hubei, 442000, China

    Jian Gu, Che Zhang, Rongguang Chen, Jun Pan, Yong Wang, Meng Ming, Weixing Gui & Dabin Wang

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  1. Jian Gu
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  2. Che Zhang
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  3. Rongguang Chen
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  4. Jun Pan
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  5. Yong Wang
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  6. Meng Ming
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  7. Weixing Gui
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  8. Dabin Wang
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Correspondence to Dabin Wang.

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Gu, J., Zhang, C., Chen, R. et al. Clinical implications and prognostic value of EMMPRIN/CD147 and MMP2 expression in pediatric gliomas. Eur J Pediatr 168, 705–710 (2009). https://doi.org/10.1007/s00431-008-0828-5

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  • DOI: https://doi.org/10.1007/s00431-008-0828-5

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