Reference : Experimental anti-angiogenesis causes upregulation of genes associated with poor surviva...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
http://hdl.handle.net/2268/24058
Experimental anti-angiogenesis causes upregulation of genes associated with poor survival in glioblastoma.
English
Saidi, Ahlame [> > > >]
Javerzat, Sophie [> > > >]
Bellahcene, Akeila mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
De Vos, John [> > > >]
Bello, Lorenzo [> > > >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases >]
Deprez, Manuel mailto [Université de Liège - ULg > Département des sciences cliniques > Neuropathologie >]
Loiseau, Hugues [> > > >]
Bikfalvi, Andreas [> > > >]
Hagedorn, Martin [> > > >]
2008
International Journal of Cancer = Journal International du Cancer
Wiley Liss, Inc.
122
10
2187-98
Yes (verified by ORBi)
International
0020-7136
1097-0215
New York
NY
[en] Adult ; Astrocytoma/blood supply/metabolism/mortality ; Brain/metabolism/pathology ; Brain Neoplasms/blood supply/metabolism/mortality ; Cell Proliferation ; Elafin/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glioblastoma/blood supply/metabolism/mortality ; Glycoproteins/metabolism ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neovascularization, Pathologic ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate ; Tumor Markers, Biological/genetics/metabolism ; Up-Regulation ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/genetics/metabolism
[en] Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti-angiogenic agents used increasingly in the clinic. However, to be efficient, anti-VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti-angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti-angiogenic condition in vivo, we transfected human glioma cells with short-interfering RNAs against VEGF-A and implanted them on the chick chorio-allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrixtrade mark GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL-40, a putative prognosticator for various diseases, including cancer, were strongly up-regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low-grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin-positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti-angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets.
Giga-Cancer
European Commission (STROMA) ; La Ligue contre le Cancer ; Comité de la Dordogne ; L'Agence Nationale de la Recherche (ANR)
http://hdl.handle.net/2268/24058
10.1002/ijc.23313
(c) 2008 Wiley-Liss, Inc.

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