Skip to main content

Advertisement

Log in

Midkine is highly expressed in neuroblastoma tissues

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Purpose

Neuroblastoma (NBL) is a tumor from neural crest cells, and is the most frequent solid tumor in children. Midkine (MK) is a pleiotropin analogon, which is frequently expressed in neuronal and epithelial tumors and is a marker for a poor clinical outcome. The aims of this study were to assess MK expression in NBL and investigate the correlation with clinical outcome.

Methods

Fifty-six specimens of NBL were stained for MK on a tissue microarray by immunohistochemistry (IHC). Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for MK-mRNA expression was performed. Survival data, risk factors and disease stages were correlated with MK status assessed by IHC and RT-PCR analysis.

Results

MK-mRNA expression was found in the majority of the tumor tissues (75%), whereas MK protein could be detected only in 46% of the NBL by IHC. No correlation of MK status with survival, risk factors or disease stage was observed.

Conclusion

A majority of NBL express MK-mRNA, whereas not all MK mRNA positive tumors showed also a positive MK IHC staining. The high expression of MK-mRNA expression might present a promising target for new adenovirus-based gene therapeutic approaches for the treatment of NBL.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Weinstein JL, Katzenstein HM, Cohn SL (2003) Advances in the diagnosis and treatment of neuroblastoma. Oncologist 8:278–292

    Article  PubMed  Google Scholar 

  2. Evans AE, Gerson J, Schnaufer L (1976) Spontaneous regression of neuroblastoma. Natl Cancer Inst Monogr 44:49–54

    PubMed  CAS  Google Scholar 

  3. Haas D, Albin AR, Miller C (1988) Complete pathologic maturation and regression of IVS neuroblastoma without treatment. Cancer 62:818–825

    Article  PubMed  CAS  Google Scholar 

  4. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, Gerbing RB, Reynolds CP (1999) Treatment of high risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. NEJM 341:1165–1173

    Article  PubMed  CAS  Google Scholar 

  5. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F (1993) Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466–1477

    PubMed  CAS  Google Scholar 

  6. Evans AE, D’Angio GJ, Propert K, Anderson J, Hann HW (1987) Prognostic factors in neuroblastoma. Cancer 59:1853–1859

    Article  PubMed  CAS  Google Scholar 

  7. Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, Stram DO, Gerbing RB, Lukens JN, Matthay KK, Castleberry RP et al (1999) The international neuroblastoma pathology classification. Cancer 86:364–372

    Article  PubMed  CAS  Google Scholar 

  8. Riley RD, Heney D, Jones DR, Sutton AJ, Lambert PC, Abrams KR, Young B, Wailoo AJ, Burchill SA (2004) A systematic review of molecular and biological markers in neuroblastoma. Clin Cancer Res 10:4–12

    Article  PubMed  CAS  Google Scholar 

  9. Fidler IJ (1992) Critical determinants of metastasis. Semin Cancer Biol 12:89–96

    Article  Google Scholar 

  10. Kadomatsu K, Muramatsu T (2004) Midkine and pleiotropin in neural development and cancer. Cancer Lett 204:127–143

    Article  PubMed  CAS  Google Scholar 

  11. Muramatsu T (2002) Midkine and pleiotropin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem (Tokyo) 132:359–371

    CAS  Google Scholar 

  12. Owada K, Sanjo N, Kobayashi T, Mizusawa H, Muramatsu H, Muramatsu T, Michikawa M (1999) Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons. J Neurochem 73:2084–2092

    PubMed  CAS  Google Scholar 

  13. Shimada H, Nabeya Y, Okazumi S, Matsubara H, Kadomatsu K, Muramatsu T, Ikematsu S, Sakuma S, Ochiai T (2003) Increased serum midkine concentration is a possible tumor marker in patients with superficial esophageal cancer. Ocol Rep 10:411–414

    CAS  Google Scholar 

  14. Obata Y, Kikuchi S, Lin Y, Yagyu K, Muramatsu T, Kumai H (2005) Serum midkine concentrations and gastric cancer. Cancer Sci 96:1792–1797

    Google Scholar 

  15. Ye C, Qi M, Fan QW, Ito K, Akiyama S, Kasai Y, Matsuyama M, Muramatsu T, Kadomatsu K (1999) Expression of midkine in early stage of carcinogenesis in human colorectal cancer. Br J Cancer 79:179–184

    Article  PubMed  CAS  Google Scholar 

  16. Friedrich C, Holtkamp N, Cinatl J Jr, Sakuma S, Mautner VF, Wellmann S, Michaelis M, Henze G, Kurtz A, Driever PH (2005) Overexpression of midkine in malignant peripheral nerve sheath tumor cells inhibits apoptosis and increases andiogenic potency. Int J Oncol 27:1433–1440

    PubMed  CAS  Google Scholar 

  17. Adachi Y, Reynolds PN, Yamamoto M, Wang M, Takayama K, Matsubara S, Muramatsu T, Curiel DT (2001) A midkine promotor-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow purging. Cancer Res 61:7882–7888

    PubMed  CAS  Google Scholar 

  18. Nakagawara A, Milbrandt J, Muramatsu T, Deuel TF, Zhao H, Cnaan A, Brodeur GM (1995) Differential expression of pleiotropin and midkine in advanced neuroblastomas. Cancer Res 55:1792–1797

    PubMed  CAS  Google Scholar 

  19. Ikematsu S, Nakagawara A, Nakamura Y, Sakuma S, Wakai K, Muramatsu T, Kadomatsu K (2003) Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastoma. Br J Cancer 88:1522–1526

    Article  PubMed  CAS  Google Scholar 

  20. Muramatsu H, Shirahama H, Yonezawa S, Maruta H, Muramatsu T (1993) Midkine, a retinoic acid-inducible growth/differentiation factor: immunochemical evidence for the function and distribution. Dev Biol 159:392–402

    Article  PubMed  CAS  Google Scholar 

  21. Aridome K, Takao S, Kaname T, Kadomatsu K, Natsugoe S, Kijima F, Aikou T, Muramatsu T (1998) Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas. Br J Cancer 78:472–477

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mrs. Beate Roth, the medical student Mrs. E. Varol and Mrs. A. Krickhahn, Dept. Pediatric Surgery, Universitätsklinikum Hamburg-Eppendorf, and Mr. A. Looft, Dept. Pediatric Hematology and Oncology, Universitätsklinikum Hamburg-Eppendorf for technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Henning C. Fiegel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fiegel, H.C., Kaifi, J.T., Wachowiak, R. et al. Midkine is highly expressed in neuroblastoma tissues. Pediatr Surg Int 24, 1355–1359 (2008). https://doi.org/10.1007/s00383-008-2263-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-008-2263-0

Keywords

Navigation