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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancer cell metabolism tumor microenvironment endothelial cell metabolism tumor endothelial cells heme metabolism FLVCR1a Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d04c303df48c472090ebde6173a53cfd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d04c303df48c472090ebde6173a53cfd
record_format	dspace
spelling	oai:doaj.org-article:d04c303df48c472090ebde6173a53cfd2021-11-25T16:49:00ZEndothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment10.3390/biomedicines91115572227-9059https://doaj.org/article/d04c303df48c472090ebde6173a53cfd2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1557https://doaj.org/toc/2227-9059The 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.Sara PetrilloFrancesco De GiorgioJoanna KopeckaTullio GenovaVeronica FioritoAnna Lucia AlloccoFrancesca BertinoDeborah ChiabrandoFederico MussanoFiorella AltrudaLuca MunaronChiara RigantiEmanuela TolosanoMDPI AGarticlecancer cell metabolismtumor microenvironmentendothelial cell metabolismtumor endothelial cellsheme metabolismFLVCR1aBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1557, p 1557 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cell metabolism tumor microenvironment endothelial cell metabolism tumor endothelial cells heme metabolism FLVCR1a Biology (General) QH301-705.5
spellingShingle	cancer cell metabolism tumor microenvironment endothelial cell metabolism tumor endothelial cells heme metabolism FLVCR1a Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	endothelial heme dynamics drive cancer cell metabolism by shaping the tumor microenvironment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d04c303df48c472090ebde6173a53cfd
work_keys_str_mv	AT sarapetrillo endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT francescodegiorgio endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT joannakopecka endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT tulliogenova endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT veronicafiorito endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT annaluciaallocco endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT francescabertino endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT deborahchiabrando endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT federicomussano endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT fiorellaaltruda endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT lucamunaron endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT chiarariganti endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment AT emanuelatolosano endothelialhemedynamicsdrivecancercellmetabolismbyshapingthetumormicroenvironment
_version_	1718412983457021952

Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment

Ejemplares similares