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CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

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Pathology & Oncology Research

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.

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Acknowledgments

The authors state that neither the submitted paper nor any similar paper, in whole or in part, other than an abstract or preliminary communication, has been or will be submitted to or published in any other source.

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There is no conflict of interest to declare.

Funding

This work was supported by FAPESP projets: # 01/12898-4 and 04/12133-6.

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Authors and Affiliations

  1. 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

    Andre Macedo Bianco, Miyuki Uno, Sueli Mieko Oba-Shinjo, Thais Fernanda de Almeida Galatro, Manoel Jacobsen Teixeira & Suely Kazue Nagahashi Marie

  2. Cancer Hospital of Barretos, Pio XII Fundation, State of Sao Paulo, Sao Paulo, Brazil Rua Antenos Duarte Villela, 1331 Barretos, SP, Brazil, 14784-400

    Carlos Afonso Clara

  3. Department of Pathology, School of Medicine, University of Sao Paulo, Av. Dr. Arnaldo, 455, Sao Paulo, SP, Brazil, 01246-903

    Sergio Rosemberg & Manoel Jacobsen Teixeira

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  1. Andre Macedo Bianco
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  2. Miyuki Uno
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Correspondence to Andre Macedo Bianco.

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Bianco, A.M., Uno, M., Oba-Shinjo, S.M. et al. CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation. Pathol. Oncol. Res. 21, 229–240 (2015). https://doi.org/10.1007/s12253-014-9813-7

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