Authors:	Vewinger, Nadine Huprich, Sabrina Seidmann, Larissa Russo, Alexandra Alt, Francesca Bender, Hannah Sommer, Clemens Samuel, David Lehmann, Nadine Backes, Nora Roth, Lea Harter, Patrick N. Filipski, Katharina Faber, Jörg Paret, Claudia
Title:	IGF1R is a potential new therapeutic target for HGNET-BCOR brain tumor patients
Online publication date:	7-Nov-2019
Year of first publication:	2019
Language:	english
Abstract:	(1) Background: The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2) Methods: The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3) Results: Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class “HGNET-BCOR” and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 < 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) Conclusion: IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-218
URN:	urn:nbn:de:hebis:77-publ-594015
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 20 12
Pages or article number:	Art. 3027
Publisher:	Molecular Diversity Preservation International
Publisher place:	Basel
Issue date:	2019
ISSN:	1422-0067 1661-6596
Publisher URL:	http://dx.doi.org/10.3390/ijms20123027
Publisher DOI:	10.3390/ijms20123027
Appears in collections:	JGU-Publikationen