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Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2017 Sep 01; Vol. 76 (9), pp. 779-788. - Publication Year :
- 2017
-
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.<br /> (© 2017 American Association of Neuropathologists, Inc. All rights reserved.)
- Subjects :
- Child
Child, Preschool
Cohort Studies
Craniopharyngioma genetics
Craniopharyngioma pathology
Cyst Fluid immunology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic physiology
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Male
Microarray Analysis
Pituitary Neoplasms genetics
Pituitary Neoplasms pathology
RNA, Messenger metabolism
Receptors, Interleukin-6 genetics
Receptors, Interleukin-6 metabolism
Craniopharyngioma metabolism
Cyst Fluid metabolism
Cytokines metabolism
Pituitary Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-6578
- Volume :
- 76
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 28859336
- Full Text :
- https://doi.org/10.1093/jnen/nlx061