gms | German Medical Science

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.