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Pleiotrophin expression in astrocytic and oligodendroglial tumors and it’s correlation with histological diagnosis, microvascular density, cellular proliferation and overall survival

  • Lab. Investigation-Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background

Pleiotrophin (PTN) is a secreted cytokine with several properties related with tumor development, including differentiation, angiogenesis, invasion, apoptosis and metastasis. There is evidence that PTN has also a relevant role in primary brain neoplasms and its inactivation could be important to treatment response. Astrocytic and oligodendroglial tumors are the most frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to compare PTN expression, in astrocytomas and oligodendrogliomas and its association with the histological diagnosis, microvascular density, proliferate potential and clinical outcome.

Methods

Seventy-eight central nervous system tumors were analyzed. The histological diagnosis in accordance with WHO classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was realized with these specific antibodies: pleiotrophin, CD31 to microvascular density and Ki-67 to cell proliferation.

Results

PTN expression was significantly higher in GBM and AA when compared to PA and higher in GBM compared to DA. PTN expression did not differ between O and AO. Proliferate index and microvascular density were evaluated only in high grade tumors (AA, GBM and AO) divided in three groups according to PTN expression (low, intermediate and high). These results showed no statistical difference between PTN expression and index of cellular proliferation and neither to PTN expression and microvascular density. Overall survival (OS) analysis (months) showed similar results in high grade gliomas with different levels of PTN expression.

Conclusions

Our results suggest that PTN expression is associated with histopathological grade of astrocytomas. Proliferation rate, microvascular density and overall survival do not seem to be associated with PTN expression.

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References

  1. Bao X, Mikami T, Yamada S, Faissner A, Muramatsu T, Sugahara S (2005) Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains. J Biol Chem 280:9180–9191

    Article  PubMed  CAS  Google Scholar 

  2. Deuel TF, Zhang N, Yeh HJ, Silos-Santiago I, Wang ZY (2002) Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway. Arch Biochem Biophys 397:162–171

    Article  PubMed  CAS  Google Scholar 

  3. Laaroubi K, Delbe J, Vacherot F, Desgrandes P, Tardieu M, Jaye M, Barritault D, Courty J (1994) Mitogenic and in vitro angiogenic activity of human recombinant heparin affin regulatory peptide. Growth Factors 10:89–98

    PubMed  CAS  Google Scholar 

  4. Merenmies J, Rauvula H (1990) Molecular cloning of the 18-Kda growth-associated protein of developing brain. J Biol Chem 285:16721–16724

    Google Scholar 

  5. Bowden ET, Stoica GE, Wellstein A (2002) Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase. J Biol Chem 277:3582–3586

    Google Scholar 

  6. Jager R, List B, Knabbe C, Souttou B, Raulais D, Zeiler T, Wellstein A, Aigner A, Neubauer A, Zugmaier G (2002) Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients. Br J Cancer 86:858–863

    Article  PubMed  CAS  Google Scholar 

  7. Li G, Hu Y, Huo Y, Liu M, Freeman D, Gao J, Liu X, Wu D, Wu H (2006) PTEN deletion leads to up-regulation of a secreted growth factor pleiotrophin. J Biol Chem 281:10663–10668

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Furuta M, Shiraishi T, Okamoto H, Mineta T, Tabuchi K, Shiwa M (2004) Identification of pleiotrophin in conditioned secreted from neural stem cells by SELDI-TOF and SELDI-tandem mass spectrometry. Dev Brain Res 132:189–197

    Article  CAS  Google Scholar 

  10. Jung CG, Hida H, Nakahira K, Ikenaka K, Kim HJ, Nishino N (2004) Pleiotrophin mRNA is highly expresses in neural stem (progenitor) cells of mouse ventral mesencephalon and the product promotes production of dopaminergic neurons from embryonic stem cell-derivated nestin-positive cells. FASEB J 18:1237–1239

    PubMed  CAS  Google Scholar 

  11. Lu KV, Jong KA, Kim GY, Singh J, Dia EQ, Yoshimoto K, Wang MY, Cloughesy TF, Nelson SF, Mischel PS (2005) Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. J Biol Chem 280:26953–26964

    Article  PubMed  CAS  Google Scholar 

  12. Moon HS, Park WI, Sung SH, Choi EA, Chung HW, Woo BH (2003) Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer. Gynecol Oncol 88:289–297

    Article  PubMed  CAS  Google Scholar 

  13. Muller S, Kunkel P, Lamszus K, Ulbricht U, Lorente GA, Nelson AM, von Schack D, Chin D, Lohr SC, Westphal M, Melcher T (2003) A role for tyrosine phospatase ζ in glioma cell migration. Oncogene 22:6661–6668

    Article  PubMed  CAS  Google Scholar 

  14. Powers C, Aigner A, Stoica GE, McDonnell K, Wellstein A (2002) Pleitrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth. J Biol Chem 277:14153–14158

    Article  PubMed  CAS  Google Scholar 

  15. Sanson M, Thillet J, Hoang-Xuan K (2004) Molecular changes in gliomas. Curr Opin Oncol 16:607–613

    Article  PubMed  CAS  Google Scholar 

  16. Wu H, Barusevicius A, Babb J, Klein-Szanto AK, Godwin A, Elentsas R, Gelfand JM, Lessin S, Seykora JT (2005) Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potential. J Cutan Pathol 32:125–130

    Article  PubMed  CAS  Google Scholar 

  17. Souttou B, Juhl H, Hackenbruck J, Rockseisen M, Klomp HJ, Raulais D, Vigny M, Wellstein A (1998) Relationship between serum concentrations of the growth factor pleiotrophin and pleiotrophin-positive tumors. J Nat Cancer Inst 90:1468–1473

    Article  PubMed  CAS  Google Scholar 

  18. Mentlein M, Held-Feindt J (2002) Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas. J Neurochem 83:747–753

    Article  PubMed  CAS  Google Scholar 

  19. Ulbricht U, Brockmann MA, Aigner A, Eckerich C, Muller S, Fillbrandt R, Westphal M, Lamszus K (2003) Expression and function of the receptor of the protein tyrosine phosphatase ζ and its ligand pleiotrophin in human astrocytomas. J Neuropathol Exp Neurol 62:1265–1275

    PubMed  CAS  Google Scholar 

  20. Malerczyk C, Schulte AM, Czubayko F, Bellon L, Macejak D, Riegel AT, Wellstein A (2005) Ribozyme targeting of the growth factor pleiotrophin in established tumors: a gene therapy approach. Gene Ther 12:339–346

    Article  PubMed  CAS  Google Scholar 

  21. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225

    PubMed  Google Scholar 

  22. Zhang L, Mabuchi T, Satoh E, Maeda S, Nukui H, Naganuma H (2004) Over expression of heparin-binding growth-associated molecule in malignant glioma cells. Neurol Med Chir 44:637–645

    Article  Google Scholar 

  23. Zhang N, Zhong R, Perez-Pinera P, Herradon G, Ezquerra L, Wang ZY, Deuel TF (2006) Identification of the angiogenesis signaling domain in pleiotrophin defines a mechanism of the angiogenic switch. Biochem Biophys Res Commun 343:653–658

    Article  PubMed  CAS  Google Scholar 

  24. Foehr ED, Lorente G, Kuo J, Ram R, Nikolich K, Urfer R (2006) Targeting of the receptor protein tyrosine phosphatase β with a monclonal antibody delays tumor growth in a glioblastoma model. Cancer Res 66:2271–2278

    Article  PubMed  CAS  Google Scholar 

  25. Ulbricht U, Eckerich C, Fillbrandt R, Westphal M, Lamszus K (2006) RNA interference targeting protein tyrosine phosphatase ζ/receptor-type protein tyrosine phosphatase β supresses glioblastoma growth in vitro and in vivo. J Neurochem 98:1497–1506

    Article  PubMed  CAS  Google Scholar 

  26. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Ana Maria Anselmi Dorigan for technical assistance in immunohistochemistry. The study was supported by grants 04/14029-1 and 04/12133-6 from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo).

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Authors and Affiliations

  1. Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto of University of São Paulo (USP), Hospital das Clínicas da FMRP-USP, Campus Universitário da USP, Avenida dos Bandeirantes - 3900, Bairro Monte Alegre, 14048-900, Ribeirão Preto, São Paulo, Brazil

    Fernanda M. Peria

  2. Department of Pathology and Legal Medicine, Faculty of Medicine of Ribeirão Preto of University of São Paulo (USP), São Paulo, Brazil

    Luciano Neder

  3. Departament of Neurology, Faculty of Medicine of University of São Paulo (USP), São Paulo, Brazil

    Sueli K. N. Marie & Sueli M. Oba-Shinjo

  4. Department of Pathology, Faculty of Medicine of University of São Paulo (USP), São Paulo, Brazil

    Sergio Rosemberg

  5. Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto of University of São Paulo (USP), São Paulo, Brazil

    Benedicto O. Colli & Carlos G. Carlotti Jr

  6. Departament of Neurology, Faculty of Medicine of Federal University of São Paulo (UNIFESP), São Paulo, Brazil

    Alberto A. Gabbai, Suzana M. F. Malheiros & Oswaldo K. Okamoto

  7. Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto of University of São Paulo (USP), São Paulo, Brazil

    Marco A. Zago & Rodrigo A. Panepucci

  8. Department of Immunology, Biomedical Sciences Institute of University of São Paulo (USP), São Paulo, Brazil

    Carlos A. Moreira-Filho

  9. Albert Einstein Research and Education Institute, São Paulo, Brazil

    Carlos A. Moreira-Filho & Oswaldo K. Okamoto

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  1. Fernanda M. Peria
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  2. Luciano Neder
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  3. Sueli K. N. Marie
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Correspondence to Fernanda M. Peria.

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Peria, F.M., Neder, L., Marie, S.K.N. et al. Pleiotrophin expression in astrocytic and oligodendroglial tumors and it’s correlation with histological diagnosis, microvascular density, cellular proliferation and overall survival. J Neurooncol 84, 255–261 (2007). https://doi.org/10.1007/s11060-007-9379-2

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  • DOI: https://doi.org/10.1007/s11060-007-9379-2

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