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PARP inhibition promotes endothelial-like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry.
Fernández-Cortés, Mónica; Delgado-Bellido, Daniel; Bermúdez-Jiménez, Eloísa; Paramio, Jesús M; O'Valle, Francisco; Vinckier, Stefan; Carmeliet, Peter; Garcia-Diaz, Angel; Oliver, F Javier.
Afiliación
  • Fernández-Cortés M; Instituto de Parasitología y Biomedicina López Neyra, CSIC, Centro de Investigación Biomédica en Red de Cáncer CIBERONC, Granada, Spain.
  • Delgado-Bellido D; Instituto de Parasitología y Biomedicina López Neyra, CSIC, Centro de Investigación Biomédica en Red de Cáncer CIBERONC, Granada, Spain.
  • Bermúdez-Jiménez E; Instituto de Parasitología y Biomedicina López Neyra, CSIC, Centro de Investigación Biomédica en Red de Cáncer CIBERONC, Granada, Spain.
  • Paramio JM; Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Biomedical Research Institute I+12, University Hospital "12 de Octubre", Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • O'Valle F; Department of Pathology, Faculty of Medicine, University of Granada (UGR), Granada, Spain.
  • Vinckier S; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, & Department of Oncology and Leuven Cancer Institute (LKI), Leuven, Belgium.
  • Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, & Department of Oncology and Leuven Cancer Institute (LKI), Leuven, Belgium.
  • Garcia-Diaz A; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Oliver FJ; Instituto de Parasitología y Biomedicina López Neyra, CSIC, Centro de Investigación Biomédica en Red de Cáncer CIBERONC, Granada, Spain.
J Pathol ; 259(3): 318-330, 2023 03.
Article en En | MEDLINE | ID: mdl-36484652
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 PDGFß, 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Poli(ADP-Ribosa) Polimerasas / Melanoma Límite: Humans Idioma: En Revista: J Pathol Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Poli(ADP-Ribosa) Polimerasas / Melanoma Límite: Humans Idioma: En Revista: J Pathol Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido