gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

26. - 28.08.2015, Berlin

EGFL7 as a tool to treat malignant glioma

Meeting Abstract

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  • corresponding author presenting/speaker Mirko Schmidt - Johannes Gutenberg University School of Medicine, Institute for Microscopic Anatomy and Neurobiology, Mainz, Germany
  • author presenting/speaker Nevenka Dudvarski Stankovic - Johannes Gutenberg University School of Medicine, Institute for Microscopic Anatomy and Neurobiology, Mainz, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP52

doi: 10.3205/15dgnn76, urn:nbn:de:0183-15dgnn766

Veröffentlicht: 25. August 2015

© 2015 Schmidt et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Introduction: Patients with malignant brain tumors have a poor prognosis of survival. The most lethal form, glioblastoma multiforme (GBM), is still non-curable despite of multimodal treatments. Patients havea median survival time of less than a year. Therefore new additional treatments are desirable. Recently, we characterized the protein epidermal growth factor-like domain 7 (EGFL7) as a regulator of stem cells [1]. EGFL7 is a proangiogenic factor that acts as a matricellular protein in the extracellular matrix to promote angiogenesis by its interaction with integrins [2]. Our findings identified EGFL7 as a putative modulator of the tumor microenvironment with the potential to promote tumor neoangiogenesis.

Objectives: This study aims to unravel the role of EGFL7 and the miR-126 localized within the gene in glioblastoma multiforme in order to explore its potential application as a novel medication of malignant glioma.

Material and methods: The expression of EGFL7 in glioma biopsies was evaluated by an AffyU133Plus2 gene expression array as well as qRT-PCR. Promotor methylation studies were performed using an Illumina 450K array. In order to determine the impact of EGFL7 and miR-126 on glioma, intracranial implantation models were applied in vivo and tumor neovascularization assessed by immunohistochemistry. Mechanistical data was compiled by biochemical methods, e.g. western blot or FACS.

Results: Our data unravel a tumor grade dependent expression of EGFL7 in glioma. EGFL7 has a severe effect on glioma growth in vivo, which is driven by its effect on blood vessel formation and morphology within the tumor. Molecularly, this effect is mediated by its impact on blood vessel integrins.

Conclusions: Our findings provide evidence that EGFL7 might be exploited as a target to treat malignant glioma.


References

1.
Schmidt MH, Bicker F, Nikolic I, Meister J, Babuke T, Picuric S, Müller-Esterl W, Plate KH, Dikic I. Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal. Nat Cell Biol. 2009 Jul;11(7):873-80. DOI: 10.1038/ncb1896 Externer Link
2.
Nikolic I, Stankovic ND, Bicker F, Meister J, Braun H, Awwad K, Baumgart J, Simon K, Thal SC, Patra C, Harter PN, Plate KH, Engel FB, Dimmeler S, Eble JA, Mittelbronn M, Schäfer MK, Jungblut B, Chavakis E, Fleming I, Schmidt MH. EGFL7 ligates αvβ3 integrin to enhance vessel formation. Blood. 2013 Apr 11;121(15):3041-50. DOI: 10.1182/blood-2011-11-394882 Externer Link