Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme

Stockhausen, Marie-Thérése; Broholm, Helle; Villingshøj, Mette; Kirchhoff, Maria; Gerdes, Tommy; Kristoffersen, Karina; Kosteljanetz, Michael; Spang‐Thomsen, Mogens; Poulsen, Hans Skovgaard

doi:10.1016/j.yexcr.2011.04.001

Cited by 44 publications

(46 citation statements)

References 50 publications

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“…10,11 However, in a previous publication from our laboratory we showed that GBM cell cultures established during serum-free stem cell conditions, traditionally used for in vitro growth of neural stem cells (NSC), maintained endogenous expression of EGFR and EGFRvIII. 12 This is in line with other reports showing that GBM cultures grown during stem cell conditions maintain the geno-and phenotypes of the original tumor better than GBM cells cultured during serum-containing conditions. 13 These stem cell conditions are believed to preserve and promote growth of so-called brain cancer stem-like cells (bCSC), a population of cancer cells found in GBM which share characteristics with normal NSC.…”

Section: Introductionsupporting

confidence: 91%

“…[36][37][38] It is thus likely that EGFR also plays a role in bCSC. We have in a recent study shown that expression of EGFR and especially EGFRvIII is maintained in GBM neurosphere cultures in the presence of EGF and bFGF, 12 and others have shown that such cultures promote and preserve growth of bCSC. 13 It is, furthermore, well known that GBM cells lose the expression of EGFRvIII and overexpression of EGFR in cultures established under in vitro growth conditions which contain serum.…”

Section: Discussionmentioning

confidence: 88%

“…12 All cells were maintained as neurosphere cultures in Neurobasal®-A media (NB) (Invitrogen, 10888-022) with the following additives: N2 (17502-048), B27 (12587-010), bFGF (10 ng/ml, 13256-029), EGF (10 ng/ml, PHG0311), l-glutamine (25030-024), penicillin (50 U/ml), and streptomycin (50 μg/ml, 15070-063) (all from Invitrogen), in an atmosphere of 5% CO 2 and 21% O 2 at 37 °C. Fresh media was added twice a week and spheres were mechanically dissociated at every passage.…”

Section: Methodsmentioning

confidence: 99%

“…In this culture system, which enrich for bCSC, the cells grow as neurospheres and share characteristics with normal NSC. 25 We have recently shown that such cultures maintain important features of GBM such as expression of EGFR and EGFRvIII, 12 whereas other studies have shown that GBM cells grown during traditional cell culture conditions in the presence of serum fail to maintain EGFR and EGFRvIII expression. 10,11 In addition, it has been shown that bCSC are able to differentiate in vitro upon serum exposure.…”

Section: Serum and Ra Induce Differentiation Of Human Gbm Cellsmentioning

confidence: 99%

“…PCR reactions were optimized to distinguish between EGFR and EGFRvIII expression as previously described. 12 Primers used were: EGFR forward, 5′-TCCTTGGGAA TTTGGAAATT-3′; EGFR reverse, 5′-GGCATAGGAA TTTTCGTAGT ACAT-3′; EGFRvIII forward, 5′-ATGCGACCCT CCGGGACG-3′; EGFRvIII reverse, 5′-ATCTGTCACC ACATAATTAC CT-3′; GFAP forward, 5′-CGCTGGTAGA GATGGAGGAG-3′; GFAP reverse, 5′-CTGGGGTTAA GAAGCAGCAG-3′.…”

Section: Quantitative Real-time Pcr (Q-rt-pcr)mentioning

confidence: 99%

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Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

Stockhausen

Kristoffersen

Stobbe

et al. 2013

Cancer Biology & Therapy

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Section: Introductionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Serum and Ra Induce Differentiation Of Human Gbm Cellsmentioning

confidence: 99%

Section: Quantitative Real-time Pcr (Q-rt-pcr)mentioning

confidence: 99%

See 3 more Smart Citations

Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

Stockhausen

Kristoffersen

Stobbe

et al. 2013

Cancer Biology & Therapy

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Notch Signaling and Brain Tumors

Stockhausen

Kristoffersen

Poulsen

2012

Advances in Experimental Medicine and Biology

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Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors.

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Glioblastoma: pathology, molecular mechanisms and markers

et al. 2015

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Recent advances in genomic technology have led to a better understanding of key molecular alterations that underlie glioblastoma (GBM). The current WHO-based classification of GBM is mainly based on histologic features of the tumor, which frequently do not reflect the molecular differences that describe the diversity in the biology of these lesions. The current WHO definition of GBM relies on the presence of high-grade astrocytic neoplasm with the presence of either microvascular proliferation and/or tumor necrosis. High-throughput analyses have identified molecular subtypes and have led to progress in more accurate classification of GBM. These findings, in turn, would result in development of more effective patient stratification, targeted therapeutics, and prediction of patient outcome. While consensus has not been reached on the precise nature and means to sub-classify GBM, it is clear that IDH-mutant GBMs are clearly distinct from GBMs without IDH1/2 mutation with respect to molecular and clinical features, including prognosis. In addition, recent findings in pediatric GBMs regarding mutations in the histone H3F3A gene suggest that these tumors may represent a 3rd major category of GBM, separate from adult primary (IDH1/2 wt), and secondary (IDH1/2 mut) GBMs. In this review, we describe major clinically relevant genetic and epigenetic abnormalities in GBM-such as mutations in IDH1/2, EGFR, PDGFRA, and NF1 genes-altered methylation of MGMT gene promoter, and mutations in hTERT promoter. These markers may be incorporated into a more refined classification system and applied in more accurate clinical decision-making process. In addition, we focus on current understanding of the biologic heterogeneity and classification of GBM and highlight some of the molecular signatures and alterations that characterize GBMs as histologically defined. We raise the question whether IDH-wild type high grade astrocytomas without microvascular proliferation or necrosis might best be classified as GBM, even if they lack the histologic hallmarks as required in the current WHO classification. Alternatively, an astrocytic tumor that fits the current histologic definition of GBM, but which shows an IDH mutation may in fact be better classified as a distinct entity, given that IDH-mutant GBM are quite distinct from a biological and clinical perspective.

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Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme

Cited by 44 publications

References 50 publications

Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

Differentiation of glioblastoma multiforme stem-like cells leads to downregulation of EGFR and EGFRvIII and decreased tumorigenic and stem-like cell potential

Notch Signaling and Brain Tumors

Glioblastoma: pathology, molecular mechanisms and markers

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