Nov 9, 2018

Interleukin-8/CXCR2 signaling regulates therapy-induced plasticity and enhances tumorigenicity in glioblastoma

BioRxiv : the Preprint Server for Biology
Tanwir HasanAtique U. Ahmed

Abstract

Glioblastoma (GBM) remains one of the least treatable types of cancer. Recent work highlights two key factors contributing to this resistant phenotype cellular plasticity, the ability of GBM cells to adopt many phenotypes, and the microenvironment. Here, we provide evidence that Interleukin-8 (IL-8) plays a vital role in promoting cellular plasticity and cancer initiating cells (CICs) niche during anti-glioma chemotherapy. IL-8 expression is significantly elevated during chemotherapy, and immunohistochemical analysis of matched primary and recurrent patient GBM tissues revealed about 60% of recurrent tissues IL-8 expression is upregulated. In silico analysis of the TCGA data indicated that IL-8 signaling could promote epigenetic plasticity by altering the polycomb repressor complex activity. We are proposing that such regulation my promote epigenetic plasticity, which allows the GBM cells to adapt therapy and may promote therapeutic resistance. Our data show that IL-8 is a crucial microenvironmental factor involved in developing therapeutic adaptation and can be targeted in combination with conventional chemo- and radiotherapy to prevent disease recurrence.

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Mentioned in this Paper

Tumorigenicity
Immunohistochemistry
Transcription Repressor/Corepressor
Regulation of Biological Process
Recurrent Malignant Neoplasm
Neuronal Plasticity
Administration of Antineoplastic Agent
Study of Epigenetics
Therapeutic Radiology Procedure
Cell Plasticity

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