The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts
IntroductionOral cancer is one of the most common forms of head and neck cancers. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral malignancies. The molecular pathogenesis of OSCC is complex as it involves altered expression of specific genes and proteins, but also comprise...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1492282/full |
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| author | Aleksandra Lipka Tine M. Søland Anni I. Nieminen Dipak Sapkota Trude M. Haug Hilde K. Galtung |
| author_facet | Aleksandra Lipka Tine M. Søland Anni I. Nieminen Dipak Sapkota Trude M. Haug Hilde K. Galtung |
| author_sort | Aleksandra Lipka |
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| description | IntroductionOral cancer is one of the most common forms of head and neck cancers. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral malignancies. The molecular pathogenesis of OSCC is complex as it involves altered expression of specific genes and proteins, but also comprises changes in metabolic processes. It is suggested that extracellular vesicles (EVs) released by cancer cells may contribute to cancer development and metastasis by recruiting and changing phenotype of normal cells that surround the tumor.MethodsThe aim of the project was to characterize the effect of OSCC EVs on the metabolic profile of normal oral fibroblasts (NOFs). Targeted liquid chromatography mass spectrometry metabolic profiling was performed on control cells and NOFs exposed to OSCC EVs for 24 and 48 h.ResultsAnalysis of detected metabolites revealed that OSCC EVs affected NOFs the most after 24 h of exposure. Among metabolites that were significantly altered at 24 h, pyruvate, ATP, UTP, coenzyme A, and dihydroxyacetone phosphate were upregulated, while fatty acids such as nervonic acid, linoleate, oleate, palmitoleic acid, and docosahexaenoic acid were downregulated. These findings were supported by Western blotting of pyruvate kinase M2 (PKM2) and aldolase, fructose-bisphosphate A (ALDOA).ConclusionThe metabolic pathways of glycolysis, citric acid cycle, and amino acid metabolism were enriched, suggesting that OSCC EVs cause phenotype switch in NOFs that may contribute to acquiring a pro-tumorigenic phenotype. |
| format | Article |
| id | doaj-art-e0d02cfd3c1640208f9cade732e0720b |
| institution | OA Journals |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-e0d02cfd3c1640208f9cade732e0720b2025-08-20T02:15:30ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-02-011210.3389/fmolb.2025.14922821492282The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblastsAleksandra Lipka0Tine M. Søland1Anni I. Nieminen2Dipak Sapkota3Trude M. Haug4Hilde K. Galtung5Faculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, NorwayFaculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, NorwayInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, FinlandFaculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, NorwayFaculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, NorwayFaculty of Dentistry, Institute of Oral Biology, University of Oslo, Oslo, NorwayIntroductionOral cancer is one of the most common forms of head and neck cancers. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral malignancies. The molecular pathogenesis of OSCC is complex as it involves altered expression of specific genes and proteins, but also comprises changes in metabolic processes. It is suggested that extracellular vesicles (EVs) released by cancer cells may contribute to cancer development and metastasis by recruiting and changing phenotype of normal cells that surround the tumor.MethodsThe aim of the project was to characterize the effect of OSCC EVs on the metabolic profile of normal oral fibroblasts (NOFs). Targeted liquid chromatography mass spectrometry metabolic profiling was performed on control cells and NOFs exposed to OSCC EVs for 24 and 48 h.ResultsAnalysis of detected metabolites revealed that OSCC EVs affected NOFs the most after 24 h of exposure. Among metabolites that were significantly altered at 24 h, pyruvate, ATP, UTP, coenzyme A, and dihydroxyacetone phosphate were upregulated, while fatty acids such as nervonic acid, linoleate, oleate, palmitoleic acid, and docosahexaenoic acid were downregulated. These findings were supported by Western blotting of pyruvate kinase M2 (PKM2) and aldolase, fructose-bisphosphate A (ALDOA).ConclusionThe metabolic pathways of glycolysis, citric acid cycle, and amino acid metabolism were enriched, suggesting that OSCC EVs cause phenotype switch in NOFs that may contribute to acquiring a pro-tumorigenic phenotype.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1492282/fulloral canceroral squamous cell carcinomafibroblastsphenotypemetabolic profileextracellular vesicles |
| spellingShingle | Aleksandra Lipka Tine M. Søland Anni I. Nieminen Dipak Sapkota Trude M. Haug Hilde K. Galtung The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts Frontiers in Molecular Biosciences oral cancer oral squamous cell carcinoma fibroblasts phenotype metabolic profile extracellular vesicles |
| title | The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| title_full | The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| title_fullStr | The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| title_full_unstemmed | The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| title_short | The effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| title_sort | effect of extracellular vesicles derived from oral squamous cell carcinoma on the metabolic profile of oral fibroblasts |
| topic | oral cancer oral squamous cell carcinoma fibroblasts phenotype metabolic profile extracellular vesicles |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1492282/full |
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