title: CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation.
abstract: The CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1α expression and IDH1 mutation. CXCR7, CXCR4 and HIF1α mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1α (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1α (p = 0.008). HIF1α overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1α in GBM. Overexpression HIF1α was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.
authors: Department of Neurology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil Laboratory of Molecular and Cellular Biology, LIM15 Av. Dr. Arnaldo, 455, 4th floor, r.4110, Sao Paulo, SP, Brazil, 01246-903, abianco@usp.br.
authors: Andre Macedo
authors: AM
authors: Bianco
authors: Miyuki
authors: M
authors: Uno
authors: Sueli Mieko
authors: SM
authors: Oba-Shinjo
authors: Carlos Afonso
authors: CA
authors: Clara
authors: Thais Fernanda
authors: TF
authors: de Almeida Galatro
authors: Sergio
authors: S
authors: Rosemberg
authors: Manoel Jacobsen
authors: MJ
authors: Teixeira
authors: Suely Kazue
authors: SK
authors: Nagahashi Marie
mesh_terms: D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C501896:ACKR3 protein, human; C527276:CXCR4 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human