Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles
Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we chara...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Proteomes |
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| Online Access: | https://www.mdpi.com/2227-7382/11/1/3 |
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| author | Kathleen A. Heck Håvard T. Lindholm Barbara Niederdorfer Eirini Tsirvouli Martin Kuiper Åsmund Flobak Astrid Lægreid Liv Thommesen |
| author_facet | Kathleen A. Heck Håvard T. Lindholm Barbara Niederdorfer Eirini Tsirvouli Martin Kuiper Åsmund Flobak Astrid Lægreid Liv Thommesen |
| author_sort | Kathleen A. Heck |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we characterised the proteome landscape of sEVs and their cells of origin in three CRC cell lines HCT116, HT29 and SW620 to explore molecular traits that could be exploited as cancer biomarker candidates and how intracellular signalling can be assessed by sEV analysis instead of directly obtaining the cell of origin itself. Our findings revealed that sEV cargo clearly reflects its cell of origin with proteins of the PI3K-AKT pathway highly represented in sEVs. Proteins known to be involved in CRC were detected in both cells and sEVs including KRAS, ARAF, mTOR, PDPK1 and MAPK1, while TGFB1 and TGFBR2, known to be key players in epithelial cancer carcinogenesis, were found to be enriched in sEVs. Furthermore, the phosphopeptide-enriched profiling of cell lysates demonstrated a distinct pattern between cell lines and highlighted potential phosphoproteomic targets to be investigated in sEVs. The total proteomic and phosphoproteomics profiles described in the current work can serve as a source to identify candidates for cancer biomarkers that can potentially be assessed from liquid biopsies. |
| first_indexed | 2024-03-11T05:59:15Z |
| format | Article |
| id | doaj.art-750dbd6bcab14f79b3d6cdf8f74b1b95 |
| institution | Directory Open Access Journal |
| issn | 2227-7382 |
| language | English |
| last_indexed | 2024-03-11T05:59:15Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Proteomes |
| spelling | doaj.art-750dbd6bcab14f79b3d6cdf8f74b1b952023-11-17T13:33:22ZengMDPI AGProteomes2227-73822023-01-01111310.3390/proteomes11010003Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular VesiclesKathleen A. Heck0Håvard T. Lindholm1Barbara Niederdorfer2Eirini Tsirvouli3Martin Kuiper4Åsmund Flobak5Astrid Lægreid6Liv Thommesen7Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biology, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biology, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Biomedical Laboratory Science, Norwegian University of Science and Technology, 7491 Trondheim, NorwayColorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we characterised the proteome landscape of sEVs and their cells of origin in three CRC cell lines HCT116, HT29 and SW620 to explore molecular traits that could be exploited as cancer biomarker candidates and how intracellular signalling can be assessed by sEV analysis instead of directly obtaining the cell of origin itself. Our findings revealed that sEV cargo clearly reflects its cell of origin with proteins of the PI3K-AKT pathway highly represented in sEVs. Proteins known to be involved in CRC were detected in both cells and sEVs including KRAS, ARAF, mTOR, PDPK1 and MAPK1, while TGFB1 and TGFBR2, known to be key players in epithelial cancer carcinogenesis, were found to be enriched in sEVs. Furthermore, the phosphopeptide-enriched profiling of cell lysates demonstrated a distinct pattern between cell lines and highlighted potential phosphoproteomic targets to be investigated in sEVs. The total proteomic and phosphoproteomics profiles described in the current work can serve as a source to identify candidates for cancer biomarkers that can potentially be assessed from liquid biopsies.https://www.mdpi.com/2227-7382/11/1/3extracellular vesiclessEVsintracellular signallingproteomicsphosphoproteomicscolorectal cancer |
| spellingShingle | Kathleen A. Heck Håvard T. Lindholm Barbara Niederdorfer Eirini Tsirvouli Martin Kuiper Åsmund Flobak Astrid Lægreid Liv Thommesen Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles Proteomes extracellular vesicles sEVs intracellular signalling proteomics phosphoproteomics colorectal cancer |
| title | Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles |
| title_full | Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles |
| title_fullStr | Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles |
| title_full_unstemmed | Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles |
| title_short | Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles |
| title_sort | characterisation of colorectal cancer cell lines through proteomic profiling of their extracellular vesicles |
| topic | extracellular vesicles sEVs intracellular signalling proteomics phosphoproteomics colorectal cancer |
| url | https://www.mdpi.com/2227-7382/11/1/3 |
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