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J Neuropathol Exp Neurol. 2017 Sep 1;76(9):779-788. doi: 10.1093/jnen/nlx061.

Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

Author information

1
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Developmental Biology and Cancer Programme, Great Ormond Street UCL Institute of Child Health, London, UK; Department of Neurological Surgery, Columbia University Medical Center, New York, New York; Division of Pediatric Neurosurgery, Department of Neurosurgery, Miami Children's Hospital, University of Miami/Miller School of Medicine, Miami, Florida; Department of Neurosurgery, Stanford University Medical Center, Palo Alto, California; Department of Neurological Surgery, Weill Medical College of Cornell University and Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Neurosurgery, Children's Hospital Alabama, Birmingham, Alabama; Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pathology; Department of Neurosurgery; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Histopathology, Great Ormond Street Hospital, NHS Trust, London, UK; Morgan Adams Foundation Pediatric Brain Tumor Research Program; Pediatric Neurosurgery, Children's Hospital Colorado; and Adult and Child Center for Health Outcomes Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Abstract

Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions.

KEYWORDS:

Adamantinomatous craniopharyngioma; Craniopharyngioma cyst; Cytokine; IL-6; Immunomodulation; Inflammatory

PMID:
28859336
PMCID:
PMC6005018
DOI:
10.1093/jnen/nlx061
[Indexed for MEDLINE]
Free PMC Article

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