Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor

Autores
Suares, Alejandra Carolina; Tapia, Cinthya Mariela; González Pardo, María Verónica
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The Kaposi´s Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi?s sarcoma. Persistent expression and activity of vGPCR is required for NFB pathway activation and tumor maintenance in endothelial cells. We have previously demonstrated that 1α,25(OH)2D3 inhibits vGPCR cell growth, NFB activity and induces apoptosis in a VDR dependent manner. Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids (MCS) when cultured in suspension or a non adhesive environment. Compared to conventional mono-layer cultures (2D-cultures), MCS resemble real tissues better in terms of structural and functional properties. In this study we developed the method to obtain MCS from vGPCR cells in order to test whether MCS respond similar to 2D-cultures during 1α,25(OH)2D3. First, we found that vGPCR MCS started to form after 4 day-growth and reached a diameter of 200 µm at 12 day-growth, whereas cells without vGPCR expression remained in a starry shape. Secondly, vGPCR MCS size and architecture was analyzed during 1α,25(OH)2D3 (0-100 nM, 48 h) incubation. We found that MCS treated with 1 nM of 1α,25(OH)2D3 were compacted and began to disaggregate though no changes in their size were observed, whereas at the higher dose (100 nM) the architecture of MCS was broken. Furthermore, VDR mRNA expression increased significantly and this change was accompanied by a reduction of HIF-1α and an increase of VEGF, p21 and Bim mRNA expression. Finally, Results from Western blot analysis showed that 1α,25(OH)2D3 decreased ERK1/2 and Akt protein phosphorylation. In conclusion, these data have revealed that 1α,25(OH)2D3 inhibits vGPCR MCS proliferation and induces apoptosis similar to vGPCR 2D-cultures.Keywords: Spheroids, vGPCR cells, 1α,25(OH)2D3, anti-proliferative effects.
Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
21st Workshop on Vitamin D
Barcelona
España
University of East Anglia
Materia
VITAMINA D
ENDOTHELIAL CELL
SPHEROIDS
ANTINEOPLASIC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/159634
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptorSuares, Alejandra CarolinaTapia, Cinthya MarielaGonzález Pardo, María VerónicaVITAMINA DENDOTHELIAL CELLSPHEROIDSANTINEOPLASIChttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The Kaposi´s Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi?s sarcoma. Persistent expression and activity of vGPCR is required for NFB pathway activation and tumor maintenance in endothelial cells. We have previously demonstrated that 1α,25(OH)2D3 inhibits vGPCR cell growth, NFB activity and induces apoptosis in a VDR dependent manner. Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids (MCS) when cultured in suspension or a non adhesive environment. Compared to conventional mono-layer cultures (2D-cultures), MCS resemble real tissues better in terms of structural and functional properties. In this study we developed the method to obtain MCS from vGPCR cells in order to test whether MCS respond similar to 2D-cultures during 1α,25(OH)2D3. First, we found that vGPCR MCS started to form after 4 day-growth and reached a diameter of 200 µm at 12 day-growth, whereas cells without vGPCR expression remained in a starry shape. Secondly, vGPCR MCS size and architecture was analyzed during 1α,25(OH)2D3 (0-100 nM, 48 h) incubation. We found that MCS treated with 1 nM of 1α,25(OH)2D3 were compacted and began to disaggregate though no changes in their size were observed, whereas at the higher dose (100 nM) the architecture of MCS was broken. Furthermore, VDR mRNA expression increased significantly and this change was accompanied by a reduction of HIF-1α and an increase of VEGF, p21 and Bim mRNA expression. Finally, Results from Western blot analysis showed that 1α,25(OH)2D3 decreased ERK1/2 and Akt protein phosphorylation. In conclusion, these data have revealed that 1α,25(OH)2D3 inhibits vGPCR MCS proliferation and induces apoptosis similar to vGPCR 2D-cultures.Keywords: Spheroids, vGPCR cells, 1α,25(OH)2D3, anti-proliferative effects.Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina21st Workshop on Vitamin DBarcelonaEspañaUniversity of East AngliaElsevierHewinson, MartinFeet, James2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/159634Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor; 21st Workshop on Vitamin D; Barcelona; España; 2018; 210-2170960-0760CONICET DigitalCONICETenghttps://www.sciencedirect.com/journal/the-journal-of-steroid-biochemistry-and-molecular-biology/special-issue/10H05QXM3J1info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/journal/the-journal-of-steroid-biochemistry-and-molecular-biology/special-issue/10H05QXM3J1info:eu-repo/semantics/altIdentifier/doi/10.1016/J.JSBMB.2019.03.026Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:44:18Zoai:ri.conicet.gov.ar:11336/159634instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:44:18.444CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
title Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
spellingShingle Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
Suares, Alejandra Carolina
VITAMINA D
ENDOTHELIAL CELL
SPHEROIDS
ANTINEOPLASIC
title_short Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
title_full Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
title_fullStr Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
title_full_unstemmed Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
title_sort Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor
dc.creator.none.fl_str_mv Suares, Alejandra Carolina
Tapia, Cinthya Mariela
González Pardo, María Verónica
author Suares, Alejandra Carolina
author_facet Suares, Alejandra Carolina
Tapia, Cinthya Mariela
González Pardo, María Verónica
author_role author
author2 Tapia, Cinthya Mariela
González Pardo, María Verónica
author2_role author
author
dc.contributor.none.fl_str_mv Hewinson, Martin
Feet, James
dc.subject.none.fl_str_mv VITAMINA D
ENDOTHELIAL CELL
SPHEROIDS
ANTINEOPLASIC
topic VITAMINA D
ENDOTHELIAL CELL
SPHEROIDS
ANTINEOPLASIC
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The Kaposi´s Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi?s sarcoma. Persistent expression and activity of vGPCR is required for NFB pathway activation and tumor maintenance in endothelial cells. We have previously demonstrated that 1α,25(OH)2D3 inhibits vGPCR cell growth, NFB activity and induces apoptosis in a VDR dependent manner. Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids (MCS) when cultured in suspension or a non adhesive environment. Compared to conventional mono-layer cultures (2D-cultures), MCS resemble real tissues better in terms of structural and functional properties. In this study we developed the method to obtain MCS from vGPCR cells in order to test whether MCS respond similar to 2D-cultures during 1α,25(OH)2D3. First, we found that vGPCR MCS started to form after 4 day-growth and reached a diameter of 200 µm at 12 day-growth, whereas cells without vGPCR expression remained in a starry shape. Secondly, vGPCR MCS size and architecture was analyzed during 1α,25(OH)2D3 (0-100 nM, 48 h) incubation. We found that MCS treated with 1 nM of 1α,25(OH)2D3 were compacted and began to disaggregate though no changes in their size were observed, whereas at the higher dose (100 nM) the architecture of MCS was broken. Furthermore, VDR mRNA expression increased significantly and this change was accompanied by a reduction of HIF-1α and an increase of VEGF, p21 and Bim mRNA expression. Finally, Results from Western blot analysis showed that 1α,25(OH)2D3 decreased ERK1/2 and Akt protein phosphorylation. In conclusion, these data have revealed that 1α,25(OH)2D3 inhibits vGPCR MCS proliferation and induces apoptosis similar to vGPCR 2D-cultures.Keywords: Spheroids, vGPCR cells, 1α,25(OH)2D3, anti-proliferative effects.
Fil: Suares, Alejandra Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: González Pardo, María Verónica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
21st Workshop on Vitamin D
Barcelona
España
University of East Anglia
description The Kaposi´s Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi?s sarcoma. Persistent expression and activity of vGPCR is required for NFB pathway activation and tumor maintenance in endothelial cells. We have previously demonstrated that 1α,25(OH)2D3 inhibits vGPCR cell growth, NFB activity and induces apoptosis in a VDR dependent manner. Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids (MCS) when cultured in suspension or a non adhesive environment. Compared to conventional mono-layer cultures (2D-cultures), MCS resemble real tissues better in terms of structural and functional properties. In this study we developed the method to obtain MCS from vGPCR cells in order to test whether MCS respond similar to 2D-cultures during 1α,25(OH)2D3. First, we found that vGPCR MCS started to form after 4 day-growth and reached a diameter of 200 µm at 12 day-growth, whereas cells without vGPCR expression remained in a starry shape. Secondly, vGPCR MCS size and architecture was analyzed during 1α,25(OH)2D3 (0-100 nM, 48 h) incubation. We found that MCS treated with 1 nM of 1α,25(OH)2D3 were compacted and began to disaggregate though no changes in their size were observed, whereas at the higher dose (100 nM) the architecture of MCS was broken. Furthermore, VDR mRNA expression increased significantly and this change was accompanied by a reduction of HIF-1α and an increase of VEGF, p21 and Bim mRNA expression. Finally, Results from Western blot analysis showed that 1α,25(OH)2D3 decreased ERK1/2 and Akt protein phosphorylation. In conclusion, these data have revealed that 1α,25(OH)2D3 inhibits vGPCR MCS proliferation and induces apoptosis similar to vGPCR 2D-cultures.Keywords: Spheroids, vGPCR cells, 1α,25(OH)2D3, anti-proliferative effects.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/159634
Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor; 21st Workshop on Vitamin D; Barcelona; España; 2018; 210-217
0960-0760
CONICET Digital
CONICET
url http://hdl.handle.net/11336/159634
identifier_str_mv Antineoplastic effect of 1α,25(OH)2D3 in spheroids from endothelial cells transformed by Kaposi’s sarcoma-associated herpesvirus G protein coupled receptor; 21st Workshop on Vitamin D; Barcelona; España; 2018; 210-217
0960-0760
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.sciencedirect.com/journal/the-journal-of-steroid-biochemistry-and-molecular-biology/special-issue/10H05QXM3J1
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/journal/the-journal-of-steroid-biochemistry-and-molecular-biology/special-issue/10H05QXM3J1
info:eu-repo/semantics/altIdentifier/doi/10.1016/J.JSBMB.2019.03.026
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
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rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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