PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

Galactose-induced metabolic adaptation and stem cell enrichment in small cell lung carcinoma cell lines

Name of the presenter

Sztankovics Dániel

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Authors

Dániel Sztankovics¹, Fatime Szalai¹, Dorottya Moldvai¹, Viktória Varga¹, Titanilla Dankó¹, Ágnes Czeti¹, Gábor Szalóki¹, Gábor Barna¹, Katalin Mészáros², Ildikó Krencz¹, Anna Sebestyén¹

1: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2: Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction. There have been no major advances in treating small cell lung carcinoma (SCLC) in recent decades, and platinum-based chemotherapy remains the cornerstone of therapy. Like other malignancies, SCLC is characterised by high intratumoral heterogeneity, which significantly contributes to developing therapeutic resistance and selecting resistant clones. A rare and heterogeneous subpopulation of tumour cells, known as cancer stem cells (CSCs) or quiescent cells, has been implicated in tumour progression, relapse, and metastasis. These cells exhibit chemoresistance, metastatic potential, and high metabolic plasticity.
Aims. Our work aimed to characterise the quantitative and metabolic changes in cells expressing CSC markers.
Methods. Human SCLC cell lines (H841, H196, H146) were cultured in vitro in glucose-depleted medium supplemented with galactose. Flow cytometry was used to monitor changes in the expression of CSC markers (CD24, CD44, CD133 expression, and aldehyde dehydrogenase 1 (ALDH1) activity) in response to alternative nutrient sources. The anti-proliferative effects of cisplatin, as well as various metabolic and mTOR inhibitors, were assessed using the alamarBlueTM (AB) and sulforhodamine B (SRB) assays. Liquid chromatography-mass spectrometry (LC-MS) was used to determine changes in intracellular metabolite concentrations.
Result. CD44 expression increased in the presence of galactose in all cell lines tested in vitro. Two cell lines also exhibited distinct subpopulations with stem cell markers: a CD133-positive population in H841 and a CD24/CD44 double-positive population in H196. In parallel, we also observed proliferative changes and metabolic rearrangements, shifting from the Warburg phenotype to the oxidative phosphorylation (OXPHOS) phenotype, associated with galactose consumption.
Conclusion. Our results suggest that galactose, as an alternative nutrient source, induces an OXPHOS-driven metabolic rearrangement in the investigated cell lines and promotes the enrichment of stem cell phenotypic features, facilitating the study of therapeutically resistant subpopulations in vitro.
Funding. TKP2021-EGA-24 [A.S.], NKFI-K-142799 [A.S.], NKFI-PD-146373 [I.K.], 2024-2.1.1-EKÖP-2024-00004 [D.S., F.S., D.M., V.V.], EFOP-3.6.3-VEKOP-16-2017-00009 [F.S., D.M., V.V.]