PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry

Vasculogenic mimicry (VM) describes the ability of highly aggressive tumor cells to develop pseudovascular structures without the participation of endothelial cells. PARP1 is implicated in the activation of hypoxia-inducible factors, which are crucial in tumor neovascularization. We have explored th...

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Autores: Fernández-Cortés, Mónica, Delgado-Bellido, Daniel, Bermúdez-Jiménez, Eloísa, Paramio, Jesús M., O'Valle, Francisco, Vinckier, Stefan, Carmeliet, Peter, García-Díaz, Ángel, Oliver, Francisco Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/354852
Acceso en línea:http://hdl.handle.net/10261/354852
Access Level:acceso abierto
Palabra clave:vasculogenic mimicry
tumor vasculature
PARP inhibitors
olaparib
melanoma
pericytes
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spelling PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicryFernández-Cortés, MónicaDelgado-Bellido, DanielBermúdez-Jiménez, EloísaParamio, Jesús M.O'Valle, FranciscoVinckier, StefanCarmeliet, PeterGarcía-Díaz, ÁngelOliver, Francisco Javiervasculogenic mimicrytumor vasculaturePARP inhibitorsolaparibmelanomapericytesVasculogenic mimicry (VM) describes the ability of highly aggressive tumor cells to develop pseudovascular structures without the participation of endothelial cells. PARP1 is implicated in the activation of hypoxia-inducible factors, which are crucial in tumor neovascularization. We have explored the role of hypoxia and PARP inhibition in VM. In uveal melanoma xenografts, the PARP inhibitor olaparib improved in vivo pericyte coverage specifically of VM channels. This was concomitant with reduced metastasis in olaparib-treated VM tumors. PARP inhibition and hypoxia modulated melanoma tube formation in vitro, inducing a more sparse and regular tubular architecture. Whole-transcriptome profiling revealed that olaparib treatment under hypoxic conditions modulated the expression of genes implicated in vasculogenesis during tube formation, enhancing the endothelial-like phenotype of VM uveal melanoma cells. PARP inhibition, especially during hypoxia, upregulated PDGFβ, which is essential for pericyte recruitment. Our study indicates that PARP inhibitors may enhance the endothelial characteristics of VM cells, modulate pericyte coverage, and reduce metastatic spread in VM melanoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.RNA sequencing and bioinformatics analyses were carried out at the Instituto de Parasitología y Biomedicina ‘López-Neyra’ (IPBLN-CSIC) in the Genomics and Bioinformatics Units. This work was supported by the Spanish Ministry of Economy and Competitiveness and the Spanish Ministry of Science and Innovation, SAF2015-70520-R, RTI2018-098968-B-I00, RTICC RD12/0036/0026, and CIBER Cáncer ISCIII CB16/12/00421; a grant from Junta de Andalucía, PY20_01179; and Fundación Domingo Martínez to FJO.John Wiley & SonsMinisterio de Ciencia e Innovación (España)Ministerio de Economía y Competitividad (España)Junta de AndalucíaFundación Domingo MartínezConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/354852reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1002/path.6043Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3548522026-05-22T06:33:51Z
dc.title.none.fl_str_mv PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
title PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
spellingShingle PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
Fernández-Cortés, Mónica
vasculogenic mimicry
tumor vasculature
PARP inhibitors
olaparib
melanoma
pericytes
title_short PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
title_full PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
title_fullStr PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
title_full_unstemmed PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
title_sort PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry
dc.creator.none.fl_str_mv Fernández-Cortés, Mónica
Delgado-Bellido, Daniel
Bermúdez-Jiménez, Eloísa
Paramio, Jesús M.
O'Valle, Francisco
Vinckier, Stefan
Carmeliet, Peter
García-Díaz, Ángel
Oliver, Francisco Javier
author Fernández-Cortés, Mónica
author_facet Fernández-Cortés, Mónica
Delgado-Bellido, Daniel
Bermúdez-Jiménez, Eloísa
Paramio, Jesús M.
O'Valle, Francisco
Vinckier, Stefan
Carmeliet, Peter
García-Díaz, Ángel
Oliver, Francisco Javier
author_role author
author2 Delgado-Bellido, Daniel
Bermúdez-Jiménez, Eloísa
Paramio, Jesús M.
O'Valle, Francisco
Vinckier, Stefan
Carmeliet, Peter
García-Díaz, Ángel
Oliver, Francisco Javier
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Ministerio de Economía y Competitividad (España)
Junta de Andalucía
Fundación Domingo Martínez
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv vasculogenic mimicry
tumor vasculature
PARP inhibitors
olaparib
melanoma
pericytes
topic vasculogenic mimicry
tumor vasculature
PARP inhibitors
olaparib
melanoma
pericytes
description Vasculogenic mimicry (VM) describes the ability of highly aggressive tumor cells to develop pseudovascular structures without the participation of endothelial cells. PARP1 is implicated in the activation of hypoxia-inducible factors, which are crucial in tumor neovascularization. We have explored the role of hypoxia and PARP inhibition in VM. In uveal melanoma xenografts, the PARP inhibitor olaparib improved in vivo pericyte coverage specifically of VM channels. This was concomitant with reduced metastasis in olaparib-treated VM tumors. PARP inhibition and hypoxia modulated melanoma tube formation in vitro, inducing a more sparse and regular tubular architecture. Whole-transcriptome profiling revealed that olaparib treatment under hypoxic conditions modulated the expression of genes implicated in vasculogenesis during tube formation, enhancing the endothelial-like phenotype of VM uveal melanoma cells. PARP inhibition, especially during hypoxia, upregulated PDGFβ, which is essential for pericyte recruitment. Our study indicates that PARP inhibitors may enhance the endothelial characteristics of VM cells, modulate pericyte coverage, and reduce metastatic spread in VM melanoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/354852
url http://hdl.handle.net/10261/354852
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1002/path.6043
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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