Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment
The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In...
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MDPI AG
2021-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1557 |
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| author | Sara Petrillo Francesco De Giorgio Joanna Kopecka Tullio Genova Veronica Fiorito Anna Lucia Allocco Francesca Bertino Deborah Chiabrando Federico Mussano Fiorella Altruda Luca Munaron Chiara Riganti Emanuela Tolosano |
| author_facet | Sara Petrillo Francesco De Giorgio Joanna Kopecka Tullio Genova Veronica Fiorito Anna Lucia Allocco Francesca Bertino Deborah Chiabrando Federico Mussano Fiorella Altruda Luca Munaron Chiara Riganti Emanuela Tolosano |
| author_sort | Sara Petrillo |
| collection | DOAJ |
| description | The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy. |
| first_indexed | 2024-03-10T05:41:39Z |
| format | Article |
| id | doaj.art-d04c303df48c472090ebde6173a53cfd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:39Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d04c303df48c472090ebde6173a53cfd2023-11-22T22:29:59ZengMDPI AGBiomedicines2227-90592021-10-01911155710.3390/biomedicines9111557Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor MicroenvironmentSara Petrillo0Francesco De Giorgio1Joanna Kopecka2Tullio Genova3Veronica Fiorito4Anna Lucia Allocco5Francesca Bertino6Deborah Chiabrando7Federico Mussano8Fiorella Altruda9Luca Munaron10Chiara Riganti11Emanuela Tolosano12Molecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyDepartment of Oncology, University of Torino, 10126 Torino, ItalyDepartment of Life Sciences and Systems Biology, University of Torino, 10123 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyDepartment of Surgical Sciences, C.I.R. Dental School, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyDepartment of Life Sciences and Systems Biology, University of Torino, 10123 Torino, ItalyDepartment of Oncology, University of Torino, 10126 Torino, ItalyMolecular Biotechnology Center (MBC), Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, ItalyThe crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy.https://www.mdpi.com/2227-9059/9/11/1557cancer cell metabolismtumor microenvironmentendothelial cell metabolismtumor endothelial cellsheme metabolismFLVCR1a |
| spellingShingle | Sara Petrillo Francesco De Giorgio Joanna Kopecka Tullio Genova Veronica Fiorito Anna Lucia Allocco Francesca Bertino Deborah Chiabrando Federico Mussano Fiorella Altruda Luca Munaron Chiara Riganti Emanuela Tolosano Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment Biomedicines cancer cell metabolism tumor microenvironment endothelial cell metabolism tumor endothelial cells heme metabolism FLVCR1a |
| title | Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment |
| title_full | Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment |
| title_fullStr | Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment |
| title_full_unstemmed | Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment |
| title_short | Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment |
| title_sort | endothelial heme dynamics drive cancer cell metabolism by shaping the tumor microenvironment |
| topic | cancer cell metabolism tumor microenvironment endothelial cell metabolism tumor endothelial cells heme metabolism FLVCR1a |
| url | https://www.mdpi.com/2227-9059/9/11/1557 |
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