PhD Scientific Days 2026

Poster Session 3.W - Pharmaceutical Sciences and Health Technologies

GD2 as a Moving Target: TGF-β–Driven Ganglioside Remodeling in Glioblastoma

Name of the presenter

Tarnóczi, Katinka

Institute/workplace of the presenter

Department of Pharmacodynamics

Authors

Katinka Tarnóczi¹, Alexandra Paszternák¹, Clara Siddi², Clément Delannoy², Yann Guerardel², Tamás Tábi¹, Éva Szökő¹, Sophie Groux-Degroote²
1: Semmelweis University
2: Université de Lille

Text of the abstract

Introduction
Glioblastoma is characterized by pronounced cellular plasticity driven by microenvironmental signals such as TGF-β. While transcriptional regulation of epithelial–mesenchymal transition (EMT) has been extensively studied, the contribution of cell surface glycosphingolipids, including gangliosides, to these processes remains poorly understood.

Aims
This study aimed to investigate how TGF-β signaling modulates ganglioside composition, with a particular focus on GD2, and to assess the functional consequences of these changes in glioblastoma cell models.

Methods
U87 and U251 glioblastoma cells were analyzed using an integrated approach combining MALDI mass spectrometry, flow cytometry, quantitative PCR, and Western blotting. EMT-associated markers, ganglioside biosynthetic enzymes, and cell surface ganglioside expression were assessed following TGF-β treatment. Functional consequences were evaluated using wound healing and transwell migration assays. Pharmacological inhibition of glycosphingolipid biosynthesis was applied to determine pathway involvement.

Results
U87 and U251 cells exhibited distinct baseline ganglioside profiles. TGF-β induced cell line–specific remodeling of ganglioside biosynthesis, resulting in increased GD2 expression in U251 cells and decreased GD2 levels in U87 cells. These molecular changes were associated with divergent migratory responses: TGF-β enhanced migration in U251 cells, whereas U87 cells displayed a more limited response. Inhibition of ganglioside biosynthesis reduced GD2 expression and attenuated TGF-β–induced migration, particularly in U251 cells. Cell viability remained above 80% under all conditions, indicating that the observed effects were not due to cytotoxicity.

Conclusion
Our findings demonstrate that ganglioside remodeling represents a dynamic and context-dependent component of TGF-β–induced cellular plasticity in glioblastoma. GD2 emerges as a regulated, rather than static, surface marker with functional relevance to migratory behavior.

Funding
This work was supported by the MOBLILEX mobility program and the SE250+ Excellence Program of Semmelweis University.