Correliation Between Osteopontin Protein Expression and Histological Grade of Astrocytomas

Toy, Hatice; Yavas, Ozlem; Eren, Orhan Önder; Genç, Mine; Yavaş, Çağdaş

doi:10.1007/s12253-008-9130-0

Cited by 26 publications

(16 citation statements)

References 14 publications

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“…We found significant up-regulation in the expression of 6 out of 7 genes in the tumors induced by HRasV12/AKT in and Ngn2 (Supplementary Figure 6). Among the 6 up-regulated genes, SPP1, which has been suggested as a diagnostic marker to distinguish ATRT from PNET and medulloblastoma (34) and as grade indicator of glioma (35), showed the greatest up-regulation (6.6 fold). The pattern of gene up-regulation combined with the histological features suggest that the tumors induced by HRasV12/AKT in combination with Ngn2 or NeuroD1 are ATRT-like tumors.…”

Section: Resultsmentioning

confidence: 99%

Contribution of Tumor Heterogeneity in a New Animal Model of CNS Tumors

Chen

Becker

LoTurco

2014

Molecular Cancer Research

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The etiology of central nervous system (CNS) tumor heterogeneity is unclear. To clarify this issue, a novel animal model was developed of glioma and atypical teratoid/rhabdoid-like tumor (ATRT) produced in rats by non-viral cellular transgenesis initiated in utero. This model system affords the opportunity for directed oncogene expression, clonal labeling, and addition of tumor-modifying transgenes. By directing HRasV12 and AKT transgene expression in different cell populations with promoters that are active ubiquitously (CAG promoter), astrocyte-selective (GFAP promoter), or oligodendrocyte-selective (MBP promoter); thus, generating glioblastoma multiforme (GBM) and anaplastic oligoastrocytoma (AO), respectively. Importantly, the GBM and AO tumors were distinguishable at both the cellular and molecular level. Furthermore, proneural basic-helix-loop-helix (bHLH) transcription factors, Ngn2 (NEUROG2) or NeuroD1, were expressed along with HRasV12 and AKT in neocortical radial glia, leading to the formation of highly lethal atypical teratoid/rhabdoid-like tumors (ATRT). This study establishes a unique model in which determinants of CNS tumor diversity can be parsed out and reveals that both mutation and expression of neurogenic bHLH transcription factors contributes to CNS tumor diversity.

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Section: Resultsmentioning

confidence: 99%

Contribution of Tumor Heterogeneity in a New Animal Model of CNS Tumors

Chen

Becker

LoTurco

2014

Molecular Cancer Research

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“…4B and C). Because the product of one of these genes ( Spp1 ) has been suggested as diagnostic marker to distinguish AT/RTs from medulloblastoma (28) and as glioma grade indicator (29), we tested its expression at the protein level. Immunostainings confirmed the differential Spp1 expression (table in Fig.…”

Section: Resultsmentioning

confidence: 99%

Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells

et al. 2012

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Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors.

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“…Transcriptional regulation of OPN is complex and involves multiple pathways, including AP-1, Myc, v-Src, Runx/CBF, TGF-β/BMPs/Smad/Hox, and Wnt/β-catenin/APC/GSK-3β/Tcf-4 (29). OPN expression has been found to correlate with tumor progression in astrocytoma with high levels in GBM (33)(34)(35). OPN levels detected by immunohistochemistry identified that high cytoplasmic OPN expression correlates with poor patient survival (36).…”

Section: Cancer Epidemiol Biomarkers Prev; 19(6) June 2010mentioning

confidence: 99%

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

Sreekanthreddy

Srinivasan

Kumar

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

121

110

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Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM).Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients.Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis.Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs.Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis. Cancer Epidemiol Biomarkers Prev; 19(6); 1409-22. ©2010 AACR.

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Correliation Between Osteopontin Protein Expression and Histological Grade of Astrocytomas

Cited by 26 publications

References 14 publications

Contribution of Tumor Heterogeneity in a New Animal Model of CNS Tumors

Contribution of Tumor Heterogeneity in a New Animal Model of CNS Tumors

Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells

Identification of Potential Serum Biomarkers of Glioblastoma: Serum Osteopontin Levels Correlate with Poor Prognosis

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