Stroma-derived miR-214 coordinates tumor dissemination.

BACKGROUND Tumor progression is based on a close interaction between cancer cells and Tumor MicroEnvironment (TME). Here, we focus on the role that Cancer Associated Fibroblasts (CAFs), Mesenchymal Stem Cells (MSCs) and microRNAs (miRs) play in breast cancer and melanoma malignancy. METHODS We used...

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Autores: Orso, Francesca, Virga, Federico, Dettori, Daniela, Dalmasso, Alberto, Paradzik, Mladen, Savino, Aurora, Pomatto, Margherita A C, Quirico, Lorena, Cucinelli, Stefania, Coco, Martina, Mareschi, Katia, Fagioli, Franca, Salmena, Leonardo, Camussi, Giovanni, Provero, Paolo, Poli, Valeria, Mazzone, Massimiliano, Pandolfi, Pier Paolo, Taverna, Daniela
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16618
Acceso en línea:http://hdl.handle.net/20.500.12105/16618
Access Level:acceso abierto
Palabra clave:MicroRNAs
Breast Neoplasms
Mesenchymal Stem Cells
Humans
Animals
Mice
Female
Signal Transduction
Stromal Cells
Tumor Microenvironment
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spelling Stroma-derived miR-214 coordinates tumor dissemination.Orso, FrancescaVirga, FedericoDettori, DanielaDalmasso, AlbertoParadzik, MladenSavino, AuroraPomatto, Margherita A CQuirico, LorenaCucinelli, StefaniaCoco, MartinaMareschi, KatiaFagioli, FrancaSalmena, LeonardoCamussi, GiovanniProvero, PaoloPoli, ValeriaMazzone, MassimilianoPandolfi, Pier PaoloTaverna, DanielaMicroRNAsBreast NeoplasmsMesenchymal Stem CellsHumansAnimalsMiceFemaleSignal TransductionStromal CellsTumor MicroenvironmentBACKGROUND Tumor progression is based on a close interaction between cancer cells and Tumor MicroEnvironment (TME). Here, we focus on the role that Cancer Associated Fibroblasts (CAFs), Mesenchymal Stem Cells (MSCs) and microRNAs (miRs) play in breast cancer and melanoma malignancy. METHODS We used public databases to investigate miR-214 expression in the stroma compartment of primary human samples and evaluated tumor formation and dissemination following tumor cell injections in miR-214 overexpressing (miR-214over) and knock out (miR-214ko) mice. In addition, we dissected the impact of Conditioned Medium (CM) or Extracellular Vesicles (EVs) derived from miR-214-rich or depleted stroma cells on cell metastatic traits. RESULTS We evidence that the expression of miR-214 in human cancer or metastasis samples mostly correlates with stroma components and, in particular, with CAFs and MSCs. We present data revealing that the injection of tumor cells in miR-214over mice leads to increased extravasation and metastasis formation. In line, treatment of cancer cells with CM or EVs derived from miR-214-enriched stroma cells potentiate cancer cell migration/invasion in vitro. Conversely, dissemination from tumors grown in miR-214ko mice is impaired and metastatic traits significantly decreased when CM or EVs from miR-214-depleted stroma cells are used to treat cells in culture. Instead, extravasation and metastasis formation are fully re-established when miR-214ko mice are pretreated with miR-214-rich EVs of stroma origin. Mechanistically, we also show that tumor cells are able to induce miR-214 production in stroma cells, following the activation of IL-6/STAT3 signaling, which is then released via EVs subsequently up-taken by cancer cells. Here, a miR-214-dependent pro-metastatic program becomes activated. CONCLUSIONS Our findings highlight the relevance of stroma-derived miR-214 and its release in EVs for tumor dissemination, which paves the way for miR-214-based therapeutic interventions targeting not only tumor cells but also the TME.BioMed Central (BMC)Fondazione Cassa di Risparmio Torino CRTItalian Ministry of Health20232023-11-0220232023-01-1320232023-01-13journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/16618reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme ERCopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/166182026-06-12T12:43:37Z
dc.title.none.fl_str_mv Stroma-derived miR-214 coordinates tumor dissemination.
title Stroma-derived miR-214 coordinates tumor dissemination.
spellingShingle Stroma-derived miR-214 coordinates tumor dissemination.
Orso, Francesca
MicroRNAs
Breast Neoplasms
Mesenchymal Stem Cells
Humans
Animals
Mice
Female
Signal Transduction
Stromal Cells
Tumor Microenvironment
title_short Stroma-derived miR-214 coordinates tumor dissemination.
title_full Stroma-derived miR-214 coordinates tumor dissemination.
title_fullStr Stroma-derived miR-214 coordinates tumor dissemination.
title_full_unstemmed Stroma-derived miR-214 coordinates tumor dissemination.
title_sort Stroma-derived miR-214 coordinates tumor dissemination.
dc.creator.none.fl_str_mv Orso, Francesca
Virga, Federico
Dettori, Daniela
Dalmasso, Alberto
Paradzik, Mladen
Savino, Aurora
Pomatto, Margherita A C
Quirico, Lorena
Cucinelli, Stefania
Coco, Martina
Mareschi, Katia
Fagioli, Franca
Salmena, Leonardo
Camussi, Giovanni
Provero, Paolo
Poli, Valeria
Mazzone, Massimiliano
Pandolfi, Pier Paolo
Taverna, Daniela
author Orso, Francesca
author_facet Orso, Francesca
Virga, Federico
Dettori, Daniela
Dalmasso, Alberto
Paradzik, Mladen
Savino, Aurora
Pomatto, Margherita A C
Quirico, Lorena
Cucinelli, Stefania
Coco, Martina
Mareschi, Katia
Fagioli, Franca
Salmena, Leonardo
Camussi, Giovanni
Provero, Paolo
Poli, Valeria
Mazzone, Massimiliano
Pandolfi, Pier Paolo
Taverna, Daniela
author_role author
author2 Virga, Federico
Dettori, Daniela
Dalmasso, Alberto
Paradzik, Mladen
Savino, Aurora
Pomatto, Margherita A C
Quirico, Lorena
Cucinelli, Stefania
Coco, Martina
Mareschi, Katia
Fagioli, Franca
Salmena, Leonardo
Camussi, Giovanni
Provero, Paolo
Poli, Valeria
Mazzone, Massimiliano
Pandolfi, Pier Paolo
Taverna, Daniela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fondazione Cassa di Risparmio Torino CRT
Italian Ministry of Health
dc.subject.none.fl_str_mv MicroRNAs
Breast Neoplasms
Mesenchymal Stem Cells
Humans
Animals
Mice
Female
Signal Transduction
Stromal Cells
Tumor Microenvironment
topic MicroRNAs
Breast Neoplasms
Mesenchymal Stem Cells
Humans
Animals
Mice
Female
Signal Transduction
Stromal Cells
Tumor Microenvironment
description BACKGROUND Tumor progression is based on a close interaction between cancer cells and Tumor MicroEnvironment (TME). Here, we focus on the role that Cancer Associated Fibroblasts (CAFs), Mesenchymal Stem Cells (MSCs) and microRNAs (miRs) play in breast cancer and melanoma malignancy. METHODS We used public databases to investigate miR-214 expression in the stroma compartment of primary human samples and evaluated tumor formation and dissemination following tumor cell injections in miR-214 overexpressing (miR-214over) and knock out (miR-214ko) mice. In addition, we dissected the impact of Conditioned Medium (CM) or Extracellular Vesicles (EVs) derived from miR-214-rich or depleted stroma cells on cell metastatic traits. RESULTS We evidence that the expression of miR-214 in human cancer or metastasis samples mostly correlates with stroma components and, in particular, with CAFs and MSCs. We present data revealing that the injection of tumor cells in miR-214over mice leads to increased extravasation and metastasis formation. In line, treatment of cancer cells with CM or EVs derived from miR-214-enriched stroma cells potentiate cancer cell migration/invasion in vitro. Conversely, dissemination from tumors grown in miR-214ko mice is impaired and metastatic traits significantly decreased when CM or EVs from miR-214-depleted stroma cells are used to treat cells in culture. Instead, extravasation and metastasis formation are fully re-established when miR-214ko mice are pretreated with miR-214-rich EVs of stroma origin. Mechanistically, we also show that tumor cells are able to induce miR-214 production in stroma cells, following the activation of IL-6/STAT3 signaling, which is then released via EVs subsequently up-taken by cancer cells. Here, a miR-214-dependent pro-metastatic program becomes activated. CONCLUSIONS Our findings highlight the relevance of stroma-derived miR-214 and its release in EVs for tumor dissemination, which paves the way for miR-214-based therapeutic interventions targeting not only tumor cells but also the TME.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-11-02
2023
2023-01-13
2023
2023-01-13
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/16618
url http://hdl.handle.net/20.500.12105/16618
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme ERC
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central (BMC)
publisher.none.fl_str_mv BioMed Central (BMC)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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