Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions

McCaslin, Lana; Lagies, Simon; Mohl, Daniel A.; Plattner, Dietmar A.; Jäger, Markus; Nöthling, Claudia; Huber, Matthias C.; Juhasz-Böss, Ingolf; Kammerer, Bernd; Backhaus, Clara

doi:10.3390/ijms26199573

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Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions

by

Lana McCaslin

^1,2,

Simon Lagies

^1,3

,

Daniel A. Mohl

^1,3

,

Dietmar A. Plattner

³,

Markus Jäger

²,

Claudia Nöthling

²,

Matthias C. Huber

²,

Ingolf Juhasz-Böss

²,

Bernd Kammerer

^1,3,4,5,* and

Clara Backhaus

^2,*

¹

Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany

²

Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine—University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany

³

Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany

⁴

Signaling Research Centre BIOSS, University of Freiburg, 79104 Freiburg, Germany

⁵

Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(19), 9573; https://doi.org/10.3390/ijms26199573

Submission received: 29 August 2025 / Revised: 26 September 2025 / Accepted: 29 September 2025 / Published: 30 September 2025

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Cancer Metabolism)

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Abstract

Endometrial carcinoma (EC) is the most common malignancy of the female reproductive tract, with increasing incidence driven by aging populations and obesity. While molecular classification has improved diagnostic precision, the identification of clinically relevant metabolic biomarkers remains incomplete, and targeted therapies are not yet standardized. In this study, we investigated metabolic alterations in four EC cell lines (AN3-CA, EFE-184, HEC-1B and MFE-296) compared to non-malignant controls under normoxic and stress conditions (hypoxia and lactic acidosis) to identify metabolomic differences with potential clinical relevance. Untargeted gas chromatography–mass spectrometry (GC/MS) and targeted liquid chromatography–mass spectrometry (LC/MS) profiling revealed two distinct metabolic subtypes of EC. Cells of metabolic subtype 1 (AN3-CA and EFE-184) exhibited high biosynthetic and energy demands, enhanced cholesterol and hexosyl-ceramides synthesis and increased RNA stability, consistent with classical cancer-associated metabolic reprogramming. Cells of metabolic subtype 2 (HEC-1B and MFE-296) displayed a phospholipid-dominant metabolic profile and greater hypoxia tolerance, suggesting enhanced tumor aggressiveness and metastatic potential. Key metabolic findings were validated via real-time quantitative PCR. This study identifies and characterizes distinct metabolic subtypes of EC within the investigated cancer cell lines, thereby contributing to a better understanding of tumor heterogeneity. The results provide a basis for potential diagnostic differentiation based on specific metabolic profiles and may support the identification of novel therapeutic targets. Further validation in three-dimensional culture models and ultimately patient-derived samples is required to assess clinical relevance and integration with current molecular classifications.

Keywords: endometrial cancer; metabolic profiling; metabolic subtypes; mass spectrometry; GC/MS; LC/MS; hypoxia; lactic acidosis; cancer metabolism

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MDPI and ACS Style

McCaslin, L.; Lagies, S.; Mohl, D.A.; Plattner, D.A.; Jäger, M.; Nöthling, C.; Huber, M.C.; Juhasz-Böss, I.; Kammerer, B.; Backhaus, C. Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions. Int. J. Mol. Sci. 2025, 26, 9573. https://doi.org/10.3390/ijms26199573

AMA Style

McCaslin L, Lagies S, Mohl DA, Plattner DA, Jäger M, Nöthling C, Huber MC, Juhasz-Böss I, Kammerer B, Backhaus C. Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions. International Journal of Molecular Sciences. 2025; 26(19):9573. https://doi.org/10.3390/ijms26199573

Chicago/Turabian Style

McCaslin, Lana, Simon Lagies, Daniel A. Mohl, Dietmar A. Plattner, Markus Jäger, Claudia Nöthling, Matthias C. Huber, Ingolf Juhasz-Böss, Bernd Kammerer, and Clara Backhaus. 2025. "Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions" International Journal of Molecular Sciences 26, no. 19: 9573. https://doi.org/10.3390/ijms26199573

APA Style

McCaslin, L., Lagies, S., Mohl, D. A., Plattner, D. A., Jäger, M., Nöthling, C., Huber, M. C., Juhasz-Böss, I., Kammerer, B., & Backhaus, C. (2025). Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions. International Journal of Molecular Sciences, 26(19), 9573. https://doi.org/10.3390/ijms26199573

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Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions

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