RARE-08. CYST FLUID CYTOKINES MAY PROMOTE EPITHELIAL-TO-MESENCHYMAL TRANSITION IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA. (4th December 2020)

• Record Type: Journal Article
• Authors: Vijmasi, Trinka; Prince, Eric; Hengartner, Astrid; Agwu, Chibueze; Staulcup, Susan; Pavlova, Maryna; Griesinger, Andrea; Donson, Andrew; Dorris, Kathleen; Handler, Michael; Hankinson, Todd
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii443
• Page End: iii443
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.719
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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.