Poster Session 1.D - Pathological and Oncological Sciences
Dr. Moldvai, Dorottya, PhD
JQCZNN
Semmelweis University, Department of Pathology and Experimental Cancer Research
06203291961
moldvai.dorottya@gmail.com
Metabolic differences across 2D and 3D breast cancer models
Dorottya Moldvai1, Péter Sasvári2, Fanni Bugyi3, Ildikó Krencz1, Risa Miyaura1, Viktória Varga1, Fatime Szalai1, Zsófia Gábriel1, Gábor Barna1, Anna Sebestyén1
1: Semmelweis University, Department of Pathology and Experimental Cancer Research
2: Semmelweis University, Department of Physiology
3: HUN-REN Research Centre, MS Proteomics Research Group
Poszter
Poster Session 1.D - Pathological and Oncological Sciences
Hungarian
Pathological and Oncological Sciences
Introduction
Modernization efforts by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) aim to reduce animal experimentation in drug development by 2030. This shift increases the demand for alternative preclinical systems. However, current models remain limited: animal models often fail to replicate human biology, while 2D cultures lack tissue complexity.
Aims
This study aims to compare different experimental breast cancer models and evaluate how dimensionality and microenvironment influence cellular behavior, metabolism, and drug sensitivity.
Methods
ZR75.1 breast cancer cell line was used to establish 2D monolayers, 3D spheroids, and 3D bioprinted tissue-mimetic structures (TMSs), alongside xenograft tumors in SCID mice. Proteomic profiling was performed by LC-MS, followed by clustering and enrichment analyses. Protein expression, cell-cycle distribution, and responses to ACAT1 inhibitor (ATR-101; in vitro: 10 uM; in vivo: 3 mg/kg/day, 3x/week) and chemotherapy (doxorubicin; in vitro: 50 ng/ml; in vivo: 2 mg/kg/day, 1x/week) were also assessed among different model systems.
Results
Distinct proteomic profiles were identified across all models, emerging that dimensionality changes the metabolism of different model systems. The 3D bioprinted TMSs showed cell-cycle patterns similar to xenografts, including G₁ phase accumulation. Compared to 2D cultures, these systems displayed reduced sensitivity to ATR-101 and combination (ATR-101+doxorubicin) therapy, while long-term treatments eradicate these effects, similarly as in case of xenograft tumors.
Conclusion
Model dimensionality and extracellular context significantly affect tumor cell behavior and drug response. These findings underline the demand of the development of more physiologically relevant preclinical models.
Fundings: EKÖP-2025-00014, NKFIH-142799
email: moldvai.dorottya@gmail.com
University: Semmelweis University
Supervisor: Anna Sebestyén
Semmelweis University
Anna Sebestyén
I do not give consent to the publication of my abstract on the website of the congress.
after finishing doctoral studies with absolutorium (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
6117
16:36
16:39