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Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human meningiomas

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Abstract

We studied the expression of vascular endothelial growth factor-A (VEGF-A) and mRNA stability factor HuR in 40 supratentorial meningiomas using RT-PCR, ELISA and immunohistochemistry, and analyzed their associations with the clinicopathological characteristics, including microvascular density (MVD), peritumoral brain edema (PTBE), histological subtypes and grades, and the performance of preoperative arterial embolization. Furthermore, we investigated the involvement of HuR in the upregulation of VEGF-A expression using primary meningioma cell cultures. The level of VEGF-A is elevated in meningiomas with PTBE and in higher grade meningiomas. Preoperative arterial embolization did not significantly increase the level of VEGF-A, but it did increase the expression of HuR in tumor tissues. HuR expression was correlated positively with VEGF-A expression in meningioma tissues. In in vitro experiments, hypoxia induced the upregulation of VEGF-A expression and the cytoplasmic translocation of HuR protein in meningioma cells, and inhibition of the cytoplasmic translocation of HuR reduced the upregulation of VEGF-A expression in meningioma cells. These findings suggest that the expression of VEGF-A relates to the development of PTBE with meningiomas and the histological grade, and that HuR is involved in the upregulation of VEGF-A expression in human meningiomas.

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References

  1. Samoto K, Ikezaki K, Ono M et al (1995) Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 55:1189–1193

    PubMed  CAS  Google Scholar 

  2. Kalkanis SN, Carroll RS, Zhang J et al (1996) Correlation of vascular endothelial growth factor messenger RNA expression with peritumoral vasogenic cerebral edema in meningiomas. J Neurosurg 85:1095–1101

    PubMed  CAS  Google Scholar 

  3. Goldman CK, Bharara S, Palmer CA et al (1997) Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression. Neurosurgery 40:1269–1277

    Article  PubMed  CAS  Google Scholar 

  4. Provias J, Claffey K, delAguila L et al (1997) Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema. Neurosurgery 40:1016–1026

    Article  PubMed  CAS  Google Scholar 

  5. Bitzer M, Opitz H, Popp J et al (1998) Angiogenesis and brain oedema in intracranial meningiomas: influence of vascular endothelial growth factor. Acta Neurochir (Wien) 140:333–340

    Article  CAS  Google Scholar 

  6. Yoshioka H, Hama S, Taniguchi E et al (1999) Peritumoral brain edema associated with meningioma: influence of vascular endothelial growth factor expression and vascular blood supply. Cancer 85:936–944

    Article  PubMed  CAS  Google Scholar 

  7. Paek SH, Kim CY, Kim YY et al (2002) Correlation of clinical and biological parameters with peritumoral edema in meningioma. J Neurooncol 60:235–245

    Article  PubMed  Google Scholar 

  8. Pistolesi S, Fontanini G, Camacci T et al (2002) Meningioma-associated brain oedema: the role of angiogenic factors and pial blood supply. J Neurooncol 60:159–164

    Article  PubMed  CAS  Google Scholar 

  9. Pistolesi S, Fontanini G, Boldrini L et al (2003) The role of somatostatin in vasogenic meningioma associated brain edema. Tumori 89:136–140

    PubMed  CAS  Google Scholar 

  10. Otsuka S, Tamiya T, Ono Y et al (2004) The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas. J Neurooncol 70:349–357

    Article  PubMed  Google Scholar 

  11. Pistolesi S, Boldrini L, Gisfredi S et al (2004) Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study. Neuropathol Appl Neurobiol 30:118–125

    Article  PubMed  CAS  Google Scholar 

  12. Pietsch T, Valter MM, Wolf HK et al (1997) Expression and distribution of vascular endothelial growth factor protein in human brain tumors. Acta Neuropathol (Berl) 93:109–117

    Article  CAS  Google Scholar 

  13. Lamszus K, Lengler U, Schmidt NO et al (2000) Vascular endothelial growth factor, hepatocyte growth factor/scatter factor, basic fibroblast growth factor, and placenta growth factor in human meningiomas and their relation to angiogenesis and malignancy. Neurosurgery 46:938–947

    Article  PubMed  CAS  Google Scholar 

  14. Denizot Y, De Armas R, Caire F et al (2006) The quantitative analysis of bFGF and VEGF by ELISA in human meningiomas. Mediators Inflamm 2006:36376

    Article  PubMed  CAS  Google Scholar 

  15. Bitzer M, Wöckel L, Luft AR et al (1997) The importance of pial blood supply to the development of peritumoral brain edema in meningiomas. J Neurosurg 87:368–373

    PubMed  CAS  Google Scholar 

  16. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) WHO Classification of tumours of the central nervous system. IARC Press, Lyon

    Google Scholar 

  17. Kawano H, Hayashi M, Kabuto M et al (1988) An immunohistochemical and ultrastructural study of cultured intracranial hemangiopericytoma. Clin Neuropathol 7:105–110

    PubMed  CAS  Google Scholar 

  18. Kubota T, Hayashi M, Hasegawa M et al (1990) Extracellular matrix protein synthesis from cultured human meningioma cells. Brain Tumor Pathol 7:7–16

    Google Scholar 

  19. Ueda Y, Nakagawa T, Kubota T et al (2005) Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation. J Neurochem 95:99–110

    Article  PubMed  CAS  Google Scholar 

  20. Erkinheimo TL, Lassus H, Sivula A et al (2003) Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma. Cancer Res 63:7591–7594

    PubMed  CAS  Google Scholar 

  21. Donnini S, Machein MR, Plate KH et al (1999) Expression and localization of placenta growth factor and PlGF receptors in human meningiomas. J Pathol 189:66–71

    Article  PubMed  CAS  Google Scholar 

  22. Park K, Kim JH, Nam DH et al (2000) Vascular endothelial growth factor expression under ischemic stress in human meningiomas. Neurosci Lett 283:45–48

    Article  PubMed  CAS  Google Scholar 

  23. Yamasaki F, Yoshioka H, Hama S et al (2000) Recurrence of meningiomas. Cancer 89:1102–1110

    Article  PubMed  CAS  Google Scholar 

  24. Jensen RL, Soleau S, Bhayani MK et al (2002) Expression of hypoxia inducible factor-1 alpha and correlation with preoperative embolization of meningiomas. J Neurosurg 97:658–667

    Article  PubMed  Google Scholar 

  25. Kiliç T, Bayri Y, Ozduman K et al (2002) Tenascin in meningioma: expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape. Neurosurgery 51:183–192

    Article  PubMed  Google Scholar 

  26. Lewy-Trenda I, Omulecka A, Janczukowicz J et al (2003) The morphological analysis of vasculature and angiogenic potential in meningiomas: immunoexpression of CD31 and VEGF antibodies. Folia Neuropathol 41:149–153

    PubMed  Google Scholar 

  27. Boldrini L, Pistolesi S, Gisfredi S et al (2006) Expression of endothelin 1 and its angiogenic role in meningiomas. Virchows Arch 449:546–553

    Article  PubMed  CAS  Google Scholar 

  28. Maiuri F, De Caro Mdel B, Esposito F et al (2007) Recurrences of meningiomas: predictive value of pathological features and hormonal and growth factors. J Neurooncol 82:63–68

    Article  PubMed  Google Scholar 

  29. Tamiya T, Ono Y, Matsumoto K et al (2001) Peritumoral brain edema in intracranial meningiomas: effects of radiological and histological factors. Neurosurgery 49:1046–1051

    Article  PubMed  CAS  Google Scholar 

  30. Nakano T, Asano K, Miura H et al (2002) Meningiomas with brain edema: radiological characteristics on MRI and review of the literature. Clin Imaging 26:243–249

    Article  PubMed  Google Scholar 

  31. Takeguchi T, Miki H, Shimizu T et al (2003) Prediction of tumor-brain adhesion in intracranial meningiomas by MR imaging and DSA. Magn Reson Med Sci 2:171–179

    Article  PubMed  Google Scholar 

  32. Gurkanlar D, Er U, Sanli M et al (2005) Peritumoral brain edema in intracranial meningiomas. J Clin Neurosci 12:750–753

    Article  PubMed  Google Scholar 

  33. Bitzer M, Wöckel L, Morgalla M et al (1997) Peritumoural brain oedema in intracranial meningiomas: influence of tumour size, location and histology. Acta Neurochir (Wien) 139:1136–1142

    Article  CAS  Google Scholar 

  34. Mattei TA, Mattei JA, Ramina R et al (2005) Edema and malignancy in meningiomas. Clinics 60:201–206

    Article  PubMed  Google Scholar 

  35. Yoo H, Baia GS, Smith JS et al (2007) Expression of the hypoxia marker carbonic anhydrase 9 is associated with anaplastic phenotypes in meningiomas. Clin Cancer Res 13:68–75

    Article  PubMed  CAS  Google Scholar 

  36. Levy AP, Levy NS, Goldberg MA (1996) Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 271:2746–2753

    Article  PubMed  CAS  Google Scholar 

  37. López de Silanes I, Lal A, Gorospe M (2005) HuR: post-transcriptional paths to malignancy. RNA Biol 2:11–13

    Google Scholar 

  38. Yoo PS, Mulkeen AL, Cha CH (2006) Post-transcriptional regulation of vascular endothelial growth factor: implications for tumor angiogenesis. World J Gastroenterol 12:4937–4942

    PubMed  CAS  Google Scholar 

  39. Nabors LB, Gillespie GY, Harkins L et al (2001) HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3′ untranslated regions of cytokine and angiogenic factor mRNAs. Cancer Res 61:2154–2161

    PubMed  CAS  Google Scholar 

  40. Denkert C, Weichert W, Pest S et al (2004) Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression. Cancer Res 64:189–195

    Article  PubMed  CAS  Google Scholar 

  41. Heinonen M, Bono P, Narko K et al (2005) Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res 65:2157–2161

    Article  PubMed  CAS  Google Scholar 

  42. Mrena J, Wiksten JP, Thiel A et al (2005) Cyclooxygenase-2 is an independent prognostic factor in gastric cancer and its expression is regulated by the messenger RNA stability factor HuR. Clin Cancer Res 11:7362–7368

    Article  PubMed  CAS  Google Scholar 

  43. Cho NP, Han HS, Soh Y et al (2007) Overexpression of cyclooxygenase-2 correlates with cytoplasmic HuR expression in salivary mucoepidermoid carcinoma but not in pleomorphic adenoma. J Oral Pathol Med 36:297–303

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science to TK and TN. We are grateful to Mr. Tatsuji Hishima for his technical assistance.

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Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan

    Takahiro Sakuma, Takao Nakagawa, Kazunori Ido, Hiroaki Takeuchi, Kazufumi Sato & Toshihiko Kubota

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  1. Takahiro Sakuma
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  2. Takao Nakagawa
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  3. Kazunori Ido
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  4. Hiroaki Takeuchi
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  6. Toshihiko Kubota
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Correspondence to Takao Nakagawa.

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Sakuma, T., Nakagawa, T., Ido, K. et al. Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human meningiomas. J Neurooncol 88, 143–155 (2008). https://doi.org/10.1007/s11060-008-9559-8

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  • DOI: https://doi.org/10.1007/s11060-008-9559-8

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