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Comprehensive polar metabolomics and lipidomics profiling discriminates the transformed from the non-transformed
Caroline Rombouts1,2,3, Margot De Spiegeleer1, Lieven Van Meulebroek1
1Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Abstract:
Colorectal cancer (CRC) is the fourth most lethal disease worldwide. Despite an urgent need for therapeutic advance, selective target identification in a preclinical phase is hampered by molecular and metabolic variations between cellular models. To foster optimal model selection from a translational perspective, we performed untargeted ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry-based polar metabolomics and lipidomics to non-transformed (CCD841-CON and FHC) and transformed (HCT116, HT29, Caco2, SW480 and SW948) colon cell lines as well as tissue samples from ten colorectal cancer patients. This unveiled metabolic signatures discriminating the transformed from the non-transformed state. Metabolites involved in glutaminolysis, tryptophan catabolism, pyrimidine, lipid and carnitine synthesis were elevated in transformed cells and cancerous tissue, whereas those involved in the glycerol-3-phosphate shuttle, urea cycle and redox reactions were lowered. The degree of glutaminolysis and lipid synthesis was specific to the colon cancer cell line at hand. Thus, our study exposed pathways that are specifically associated with the transformation state and revealed differences between colon cancer cell lines that should be considered when targeting cancer-associated pathways.
Insights
Colorectal cancer (CRC) research reveals distinct metabolic signatures in transformed cells. Understanding these metabolic shifts, including glutaminolysis and lipid synthesis, is crucial for selecting appropriate preclinical models and developing targeted therapies.
Area of Science:
- Oncology
- Metabolomics
- Biochemistry
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death globally.
- Preclinical CRC research faces challenges due to metabolic variability in cellular models.
- Identifying reliable models is essential for advancing CRC therapeutics.
Purpose of the Study:
- To characterize metabolic differences between non-transformed and transformed colon cells.
- To identify metabolic signatures associated with colorectal cancer transformation.
- To guide the selection of preclinical CRC models for translational research.
Main Methods:
- Untargeted ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) based polar metabolomics and lipidomics.
- Analysis of non-transformed (CCD841-CON, FHC) and transformed (HCT116, HT29, Caco2, SW480, SW948) colon cell lines.
- Metabolomic profiling of colorectal cancer patient tissue samples.
Main Results:
- Metabolic signatures clearly distinguished transformed colon cells and cancerous tissue from non-transformed cells.
- Elevated levels of metabolites in glutaminolysis, tryptophan catabolism, pyrimidine, lipid, and carnitine synthesis were observed in transformed states.
- Decreased levels of metabolites involved in the glycerol-3-phosphate shuttle, urea cycle, and redox reactions were noted in transformed states.
- Specific cell line differences in glutaminolysis and lipid synthesis were identified.
Conclusions:
- The study identified key metabolic pathways associated with colorectal cancer transformation.
- Metabolic variations exist among different colon cancer cell lines, impacting translational research.
- These findings are critical for optimizing preclinical model selection and targeting cancer-associated pathways in CRC therapy.
