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Published in: Pediatric Surgery International 12/2008

01-12-2008 | Original Article

Midkine is highly expressed in neuroblastoma tissues

Authors: Henning C. Fiegel, Jussuf T. Kaifi, Robin Wachowiak, Alexander Quaas, Kuniaki Aridome, Keiko Ichihara-Tanaka, Takashi Muramatsu, Roman Metzger, Jakob R. Izbicki, Rudolf Erttmann, Dietrich Kluth, Holger Till

Published in: Pediatric Surgery International | Issue 12/2008

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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.
Literature
1.
go back to reference Weinstein JL, Katzenstein HM, Cohn SL (2003) Advances in the diagnosis and treatment of neuroblastoma. Oncologist 8:278–292PubMedCrossRef Weinstein JL, Katzenstein HM, Cohn SL (2003) Advances in the diagnosis and treatment of neuroblastoma. Oncologist 8:278–292PubMedCrossRef
2.
go back to reference Evans AE, Gerson J, Schnaufer L (1976) Spontaneous regression of neuroblastoma. Natl Cancer Inst Monogr 44:49–54PubMed Evans AE, Gerson J, Schnaufer L (1976) Spontaneous regression of neuroblastoma. Natl Cancer Inst Monogr 44:49–54PubMed
3.
go back to reference Haas D, Albin AR, Miller C (1988) Complete pathologic maturation and regression of IVS neuroblastoma without treatment. Cancer 62:818–825PubMedCrossRef Haas D, Albin AR, Miller C (1988) Complete pathologic maturation and regression of IVS neuroblastoma without treatment. Cancer 62:818–825PubMedCrossRef
4.
go back to reference 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 341:1165–1173PubMedCrossRef 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 341:1165–1173PubMedCrossRef
5.
go back to reference 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 11:1466–1477PubMed 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 11:1466–1477PubMed
6.
go back to reference Evans AE, D’Angio GJ, Propert K, Anderson J, Hann HW (1987) Prognostic factors in neuroblastoma. Cancer 59:1853–1859PubMedCrossRef Evans AE, D’Angio GJ, Propert K, Anderson J, Hann HW (1987) Prognostic factors in neuroblastoma. Cancer 59:1853–1859PubMedCrossRef
7.
go back to reference 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 86:364–372PubMedCrossRef 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 86:364–372PubMedCrossRef
8.
go back to reference 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 10:4–12PubMedCrossRef 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 10:4–12PubMedCrossRef
9.
go back to reference Fidler IJ (1992) Critical determinants of metastasis. Semin Cancer Biol 12:89–96CrossRef Fidler IJ (1992) Critical determinants of metastasis. Semin Cancer Biol 12:89–96CrossRef
10.
go back to reference Kadomatsu K, Muramatsu T (2004) Midkine and pleiotropin in neural development and cancer. Cancer Lett 204:127–143PubMedCrossRef Kadomatsu K, Muramatsu T (2004) Midkine and pleiotropin in neural development and cancer. Cancer Lett 204:127–143PubMedCrossRef
11.
go back to reference Muramatsu T (2002) Midkine and pleiotropin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem (Tokyo) 132:359–371 Muramatsu T (2002) Midkine and pleiotropin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem (Tokyo) 132:359–371
12.
go back to reference 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 73:2084–2092PubMed 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 73:2084–2092PubMed
13.
go back to reference 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 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
14.
go back to reference Obata Y, Kikuchi S, Lin Y, Yagyu K, Muramatsu T, Kumai H (2005) Serum midkine concentrations and gastric cancer. Cancer Sci 96:1792–1797 Obata Y, Kikuchi S, Lin Y, Yagyu K, Muramatsu T, Kumai H (2005) Serum midkine concentrations and gastric cancer. Cancer Sci 96:1792–1797
15.
go back to reference 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 79:179–184PubMedCrossRef 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 79:179–184PubMedCrossRef
16.
go back to reference 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 27:1433–1440PubMed 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 27:1433–1440PubMed
17.
go back to reference 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 61:7882–7888PubMed 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 61:7882–7888PubMed
18.
go back to reference 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 55:1792–1797PubMed 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 55:1792–1797PubMed
19.
go back to reference 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 88:1522–1526PubMedCrossRef 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 88:1522–1526PubMedCrossRef
20.
go back to reference 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 159:392–402PubMedCrossRef 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 159:392–402PubMedCrossRef
21.
go back to reference 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 78:472–477PubMed 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 78:472–477PubMed
Metadata
Title
Midkine is highly expressed in neuroblastoma tissues
Authors
Henning C. Fiegel
Jussuf T. Kaifi
Robin Wachowiak
Alexander Quaas
Kuniaki Aridome
Keiko Ichihara-Tanaka
Takashi Muramatsu
Roman Metzger
Jakob R. Izbicki
Rudolf Erttmann
Dietrich Kluth
Holger Till
Publication date
01-12-2008
Publisher
Springer-Verlag
Published in
Pediatric Surgery International / Issue 12/2008
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-008-2263-0

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