gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Inhibition of the protein tyrosine phosphatase PTP1B by the small molecule inhibitor Claramine inhibits the growth stimulation of EGF in glioblastoma cells

Inhibition der Protein Tyrosin Phosphatase PTP1B mit dem small-molecule-Inhibitor Claramine verhindert das EGF-stimulierte Wachstum von Glioblastomzellen

Meeting Abstract

  • presenting/speaker Eric Dietel - Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie, Leipzig, Deutschland
  • Frank Gaunitz - Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie, Leipzig, Deutschland
  • Jürgen Meixensberger - Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurochirurgie, Leipzig, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocP153

doi: 10.3205/22dgnc466, urn:nbn:de:0183-22dgnc4664

Published: May 25, 2022

© 2022 Dietel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Protein phosphatases, e.g., PTP1B, are crucial for regulating the activity of protein tyrosine kinases, e.g., the EGFR. Since most EGFR targeted therapies did not show a significant increase in progression-free survival and overall survival, novel ways of inhibiting tumor-promoting pathways, e.g. MAPK pathway and AKT signaling, need to be identified. Interestingly, Bartolomé and coworkers showed that the inhibition of PTP1B with Claramine prevents IL-13 induced growth and migration of GBM cells in vitro. Furthermore, PTP1B inhibition in an intracranial GBM mouse model promoted prolonged survival. The main objective of the study is the analysis of the influence of PTP1B inhibition on cell viability and growth in GBM cell lines under EGF stimulation.

Methods: 10 different glioblastoma cell lines were cultured in DMEM supplemented with 10% FCS, 2mM GlutaMax, and 1% penicillin/streptomycin. Cells were incubated with EGF (10ng/ml and 100ng/ml) and Claramine (5µM). The incubations were carried out in serum-free conditions over 48h. The CellTiter-Glo Luminescent Cell Viability Assay (CTG, Promega, Mannheim, Germany) was employed to determine viable cells by measuring ATP in cell lysates. All experiments were performed in quintuplicate. For statistical analysis, the Bonferroni multiple comparison test was used.

Results: We identified GBM cell lines responding to EGF by incubating 10 different cell lines with 10 ng/ml and 100 ng/ml EGF. The cell lines U343 (p<0.01), T98G (p<0.05), MZ18 (p<0.01), and MZ54 (p<0.01) showed a significant increase in cell viability under EGF treatment (Figure 1 [Fig. 1]). Incubation of T98G and MZ54 cells with Claramine revealed a significant reduction of cell viability treatment (MZ54 p<0.0001; T98G p<0.001). Coincubation with EGF and Claramine abolished the growth-stimulating effect of EGF in Claramine-free settings (Figure 2 [Fig. 2]).

Conclusion: These results strongly notions that Claramine's effect on viability involves signaling downstream of EGFR. Thus selective PTP1B inhibition gives the opportunity to inhibit EGFR signaling in glioblastoma cells downstream of EGFR and may thereby overcome resistances against EGFR targeted therapies.