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

Publication ,  Journal Article
Donson, AM; Apps, J; Griesinger, AM; Amani, V; Witt, DA; Anderson, RCE; Niazi, TN; Grant, G; Souweidane, M; Johnston, JM; Jackson, EM; Gore, L ...
Published in: J Neuropathol Exp Neurol
September 1, 2017

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.

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Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

September 1, 2017

Volume

76

Issue

9

Start / End Page

779 / 788

Location

England

Related Subject Headings

  • Receptors, Interleukin-6
  • RNA, Messenger
  • Pituitary Neoplasms
  • Neurology & Neurosurgery
  • Microarray Analysis
  • Male
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
 

Citation

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Donson, A. M., Apps, J., Griesinger, A. M., Amani, V., Witt, D. A., Anderson, R. C. E., … Advancing Treatment for Pediatric Craniopharyngioma                    Consortium. (2017). Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma. J Neuropathol Exp Neurol, 76(9), 779–788. https://doi.org/10.1093/jnen/nlx061
Donson, Andrew M., John Apps, Andrea M. Griesinger, Vladimir Amani, Davis A. Witt, Richard C. E. Anderson, Toba N. Niazi, et al. “Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.J Neuropathol Exp Neurol 76, no. 9 (September 1, 2017): 779–88. https://doi.org/10.1093/jnen/nlx061.
Donson AM, Apps J, Griesinger AM, Amani V, Witt DA, Anderson RCE, et al. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma. J Neuropathol Exp Neurol. 2017 Sep 1;76(9):779–88.
Donson, Andrew M., et al. “Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.J Neuropathol Exp Neurol, vol. 76, no. 9, Sept. 2017, pp. 779–88. Pubmed, doi:10.1093/jnen/nlx061.
Donson AM, Apps J, Griesinger AM, Amani V, Witt DA, Anderson RCE, Niazi TN, Grant G, Souweidane M, Johnston JM, Jackson EM, Kleinschmidt-DeMasters BK, Handler MH, Tan A-C, Gore L, Virasami A, Gonzalez-Meljem JM, Jacques TS, Martinez-Barbera JP, Foreman NK, Hankinson TC, Advancing Treatment for Pediatric Craniopharyngioma                    Consortium. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma. J Neuropathol Exp Neurol. 2017 Sep 1;76(9):779–788.
Journal cover image

Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

September 1, 2017

Volume

76

Issue

9

Start / End Page

779 / 788

Location

England

Related Subject Headings

  • Receptors, Interleukin-6
  • RNA, Messenger
  • Pituitary Neoplasms
  • Neurology & Neurosurgery
  • Microarray Analysis
  • Male
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling