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RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA

BACKGROUND: Despite poor clinical outcomes, no targeted therapies have been established for the treatment of Adamantinomatous Craniopharyngioma (ACP). The only known genetic aberration is a mutation in CTNNB1 that results in the nuclear accumulation of beta-catenin. Nuclear beta-catenin is an establ...

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Autores principales: Vijmasi, Trinka, Prince, Eric, Hengartner, Astrid, Agwu, Chibueze, Staulcup, Susan, Pavlova, Maryna, Griesinger, Andrea, Donson, Andrew, Dorris, Kathleen, Handler, Michael, Hankinson, Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715255/
http://dx.doi.org/10.1093/neuonc/noaa222.719
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author Vijmasi, Trinka
Prince, Eric
Hengartner, Astrid
Agwu, Chibueze
Staulcup, Susan
Pavlova, Maryna
Griesinger, Andrea
Donson, Andrew
Dorris, Kathleen
Handler, Michael
Hankinson, Todd
author_facet Vijmasi, Trinka
Prince, Eric
Hengartner, Astrid
Agwu, Chibueze
Staulcup, Susan
Pavlova, Maryna
Griesinger, Andrea
Donson, Andrew
Dorris, Kathleen
Handler, Michael
Hankinson, Todd
author_sort Vijmasi, Trinka
collection PubMed
description BACKGROUND: Despite poor clinical outcomes, no targeted therapies have been established for the treatment of Adamantinomatous Craniopharyngioma (ACP). The only known genetic aberration is a mutation in CTNNB1 that results in the nuclear accumulation of beta-catenin. Nuclear beta-catenin is an established inducer of Epithelial-to-Mesenchymal Transition (EMT). ACP cyst fluid is enriched with pro-inflammatory and SASP cytokines, many of which are also directly implicated in EMT. We sought to investigate the role of EMT in ACP pathology. METHODS: Normal human epithelial cells were cultured and treated with ACP cyst fluid (10%) for 1, 2, 4 and 8 days. Cell morphology was monitored by live cell brightfield microscopy. The expression of EMT associated genes, ZEB1, ZEB2, SNAI-1, SLUG, TWIST, E-Cadherin, Beta-Catenin and Vimentin was determined by RT-qPCR. RESULTS: ACP cyst fluid treated epithelial cells were markedly transformed into long, spindle-shaped cells. ACP cyst fluid treatment resulted in the progressive up-regulation of ZEB2 over 8 days (RQ=12.0; P<0.01), the progressive up-regulation of SNAI-1 over 4 days (RQ=5.1; P<0.05) and up-regulation of Vimentin (RQ=2.2; p<0.01), identified only on Day 8. CONCLUSION: ACP cyst fluid can induce EMT-like changes in normal human epithelial cells. In conjunction with the frequency of beta-catenin mutation in ACP, it is possible that EMT plays a crucial role in the pathology of ACP. Understanding ACP pathology in the context of the EMT paradigm may aid the development of new targeted therapeutics.
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spelling pubmed-77152552020-12-09 RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA Vijmasi, Trinka Prince, Eric Hengartner, Astrid Agwu, Chibueze Staulcup, Susan Pavlova, Maryna Griesinger, Andrea Donson, Andrew Dorris, Kathleen Handler, Michael Hankinson, Todd Neuro Oncol Craniopharyngioma and Rare Tumors BACKGROUND: Despite poor clinical outcomes, no targeted therapies have been established for the treatment of Adamantinomatous Craniopharyngioma (ACP). The only known genetic aberration is a mutation in CTNNB1 that results in the nuclear accumulation of beta-catenin. Nuclear beta-catenin is an established inducer of Epithelial-to-Mesenchymal Transition (EMT). ACP cyst fluid is enriched with pro-inflammatory and SASP cytokines, many of which are also directly implicated in EMT. We sought to investigate the role of EMT in ACP pathology. METHODS: Normal human epithelial cells were cultured and treated with ACP cyst fluid (10%) for 1, 2, 4 and 8 days. Cell morphology was monitored by live cell brightfield microscopy. The expression of EMT associated genes, ZEB1, ZEB2, SNAI-1, SLUG, TWIST, E-Cadherin, Beta-Catenin and Vimentin was determined by RT-qPCR. RESULTS: ACP cyst fluid treated epithelial cells were markedly transformed into long, spindle-shaped cells. ACP cyst fluid treatment resulted in the progressive up-regulation of ZEB2 over 8 days (RQ=12.0; P<0.01), the progressive up-regulation of SNAI-1 over 4 days (RQ=5.1; P<0.05) and up-regulation of Vimentin (RQ=2.2; p<0.01), identified only on Day 8. CONCLUSION: ACP cyst fluid can induce EMT-like changes in normal human epithelial cells. In conjunction with the frequency of beta-catenin mutation in ACP, it is possible that EMT plays a crucial role in the pathology of ACP. Understanding ACP pathology in the context of the EMT paradigm may aid the development of new targeted therapeutics. Oxford University Press 2020-12-04 /pmc/articles/PMC7715255/ http://dx.doi.org/10.1093/neuonc/noaa222.719 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Craniopharyngioma and Rare Tumors
Vijmasi, Trinka
Prince, Eric
Hengartner, Astrid
Agwu, Chibueze
Staulcup, Susan
Pavlova, Maryna
Griesinger, Andrea
Donson, Andrew
Dorris, Kathleen
Handler, Michael
Hankinson, Todd
RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title_full RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title_fullStr RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title_full_unstemmed RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title_short RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA
title_sort rare-08. cyst fluid cytokines may promote epithelial-to-mesenchymal transition in pediatric adamantinomatous craniopharyngioma
topic Craniopharyngioma and Rare Tumors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715255/
http://dx.doi.org/10.1093/neuonc/noaa222.719
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