CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells
ABSTRACT Several reports have demonstrated that CD147, an N‐glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. P...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Journal of Extracellular Biology |
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| Online Access: | https://doi.org/10.1002/jex2.70039 |
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| author | Filomena Colella Federica Calapà Giulia Artemi Erica Pazzaglia Rita Colonna Sara Vitale Giacomo Lazzarino Federica Vincenzoni Micol Eleonora Fiori Ruggero De Maria Sara Lucchisani Giannicola Genovese Luigi Perelli Barbara Tavazzi Alessandro Sgambato Donatella Lucchetti |
| author_facet | Filomena Colella Federica Calapà Giulia Artemi Erica Pazzaglia Rita Colonna Sara Vitale Giacomo Lazzarino Federica Vincenzoni Micol Eleonora Fiori Ruggero De Maria Sara Lucchisani Giannicola Genovese Luigi Perelli Barbara Tavazzi Alessandro Sgambato Donatella Lucchetti |
| author_sort | Filomena Colella |
| collection | DOAJ |
| description | ABSTRACT Several reports have demonstrated that CD147, an N‐glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. Previously, we showed that sEV secretion during CRC stem cell (CR‐CSCs) differentiation is partially controlled by CD147, and that CD147‐expressing sEVs (sEVs‐CD147) activate a signalling cascade in recipient cells, inducing molecular invasive features in CR‐CSCs. In the present study, we demonstrated that sEVs‐CD147 increase the expression of myofibroblast and activation markers in cancer‐associated fibroblasts (CAF). In sEVs‐CD147‐activated CAF, aerobic glycolysis was also triggered by the β‐catenin signalling pathway and induced lactate release. These effects were associated with NFKβ upregulation and NO secretion that caused increased cytokines production and VEGF release, respectively. Furthermore, co‐culture with CAF promoted CR‐CSC invasivity in vitro and tumour growth in vivo. Spatial proteomics analysis confirmed in vivo the activation of fibroblasts and the modulation of their metabolic features, within their biological context, after their conditioning with CD147‐expressing sEVs. Our findings indicate that sEV‐packaged CD147 is involved in CAF activation, thus promoting tumour progression via stroma metabolism modification. |
| format | Article |
| id | doaj-art-11d31967ee8a4a79b0776b2aad1a75c0 |
| institution | Kabale University |
| issn | 2768-2811 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj-art-11d31967ee8a4a79b0776b2aad1a75c02025-08-20T03:44:24ZengWileyJournal of Extracellular Biology2768-28112025-03-0143n/an/a10.1002/jex2.70039CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem CellsFilomena Colella0Federica Calapà1Giulia Artemi2Erica Pazzaglia3Rita Colonna4Sara Vitale5Giacomo Lazzarino6Federica Vincenzoni7Micol Eleonora Fiori8Ruggero De Maria9Sara Lucchisani10Giannicola Genovese11Luigi Perelli12Barbara Tavazzi13Alessandro Sgambato14Donatella Lucchetti15Multiplex Spatial Profiling Facility, Fondazione Policlinico Universitario ‘Agostino Gemelli’ IRCCS Rome ItalyDepartment of Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItalyDepartment of Translational Medicine and SurgeryUniversità Cattolica del Sacro CuoreRomeItalyDepartment of Translational Medicine and SurgeryUniversità Cattolica del Sacro CuoreRomeItalyDepartment of Translational Medicine and SurgeryUniversità Cattolica del Sacro CuoreRomeItalyDepartment of Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItalyUniCamillus ‐ Saint Camillus International University of Health and Medical SciencesRomeItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e PerioperatorieUniversità Cattolica del Sacro CuoreRomeItalyDepartment of Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItalyMultiplex Spatial Profiling Facility, Fondazione Policlinico Universitario ‘Agostino Gemelli’ IRCCS Rome ItalyDepartment of Oncology and Molecular MedicineIstituto Superiore di SanitàRomeItalyDepartment of Genitourinary Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSADepartment of Genitourinary Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSAUniCamillus ‐ Saint Camillus International University of Health and Medical SciencesRomeItalyMultiplex Spatial Profiling Facility, Fondazione Policlinico Universitario ‘Agostino Gemelli’ IRCCS Rome ItalyMultiplex Spatial Profiling Facility, Fondazione Policlinico Universitario ‘Agostino Gemelli’ IRCCS Rome ItalyABSTRACT Several reports have demonstrated that CD147, an N‐glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. Previously, we showed that sEV secretion during CRC stem cell (CR‐CSCs) differentiation is partially controlled by CD147, and that CD147‐expressing sEVs (sEVs‐CD147) activate a signalling cascade in recipient cells, inducing molecular invasive features in CR‐CSCs. In the present study, we demonstrated that sEVs‐CD147 increase the expression of myofibroblast and activation markers in cancer‐associated fibroblasts (CAF). In sEVs‐CD147‐activated CAF, aerobic glycolysis was also triggered by the β‐catenin signalling pathway and induced lactate release. These effects were associated with NFKβ upregulation and NO secretion that caused increased cytokines production and VEGF release, respectively. Furthermore, co‐culture with CAF promoted CR‐CSC invasivity in vitro and tumour growth in vivo. Spatial proteomics analysis confirmed in vivo the activation of fibroblasts and the modulation of their metabolic features, within their biological context, after their conditioning with CD147‐expressing sEVs. Our findings indicate that sEV‐packaged CD147 is involved in CAF activation, thus promoting tumour progression via stroma metabolism modification.https://doi.org/10.1002/jex2.70039cancer‐associated fibroblastsCD147extracellular vesiclestumour microenvironment |
| spellingShingle | Filomena Colella Federica Calapà Giulia Artemi Erica Pazzaglia Rita Colonna Sara Vitale Giacomo Lazzarino Federica Vincenzoni Micol Eleonora Fiori Ruggero De Maria Sara Lucchisani Giannicola Genovese Luigi Perelli Barbara Tavazzi Alessandro Sgambato Donatella Lucchetti CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells Journal of Extracellular Biology cancer‐associated fibroblasts CD147 extracellular vesicles tumour microenvironment |
| title | CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells |
| title_full | CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells |
| title_fullStr | CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells |
| title_full_unstemmed | CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells |
| title_short | CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells |
| title_sort | cd147 mediates the metabolic reprogramming of cancer associated fibroblasts induced by evs released by differentiating cancer stem cells |
| topic | cancer‐associated fibroblasts CD147 extracellular vesicles tumour microenvironment |
| url | https://doi.org/10.1002/jex2.70039 |
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