In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5279-5279
Abstract:
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor where local cancer cell invasion into the normal brain represents a major obstacle preventing successful therapeutic interventions. A well known mediator of invasion, proliferation and survival, is the epidermal growth factor receptor (EGFR). Amplification and subsequent over-expression of EGFR protein is the most common genetic alteration in primary GBM, with a frequency of about 40%. Of the GBMs that have an amplification of EGFR, 63-75% also show genetic rearrangements of the gene, resulting in tumors that express both the wild type, as well as mutated forms of EGFR. The most common mutation in EGFR, is the EGFRviii, were the ligand binding part of the protein is missing (del exon 2-7). This mutation leads to a constitutive activation of the protein. In patients with amplified EGFR, 50-60% also express the EGFRviii. In this work we determined a functional role of EGFRviii within invasive human GBM cells in vivo. We cultured human GBM cells, lacking EGFR amplification and EGFRviii expression, in serum-free neuro-basal (NB) medium. By orthotopic transplantation into the brains of immunodeficient rats, tumors developed that showed a highly infiltrative non-angiogenic phenotype. By over-expressing EGFRviii in these tumors, we demonstrate a robust switch towards angiogenesis as shown by dynamic-contrast enhanced MRI and by histologic verification of angiogenic vessels. Molecular analysis confirmed an up-regulation of HIF1A as well as a panel of angiogenic factors. Our results demonstrate a distinct role of EGFRviii as a vital driver of angiogenic tumor growth within human GBMs in vivo. Thus, the presented observations should have important implications for therapeutic strategies targeting EGFRviii in patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5279. doi:1538-7445.AM2012-5279
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-5279
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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