Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion

Autores
Rodriguez, Lorena Gabriela; Di Venosa, Gabriela Mariana; Rivas, Martín A.; Juarranz, Angeles; Sanz Rodriguez, Francisco; Casas, Adriana Gabriela
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aims: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methods: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findings: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. Significance: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.
Fil: Rodriguez, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
Fil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
Fil: Rivas, Martín A.. Weill Cornell Medicine; Estados Unidos
Fil: Juarranz, Angeles. Universidad Autónoma de Madrid; España
Fil: Sanz Rodriguez, Francisco. Universidad Autónoma de Madrid; España
Fil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
Materia
ACRIDINE ORANGE (PUBCHEM CID62344)
ADHESION
CHLORIN E6 (PUBCHEM CID5479494)
CISPLATIN (PUBCHEM CID5702198)
CYTOSKELETON
DOXORUBICIN (PUBCHEM CID31703)
FLUOROURACIL (PUBCHEM CID3385)
MEROCYANINE 540 (PUBCHEM CID5702743)
METHOTREXATE (PUBCHEM CID126941)
MITOMYCIN C (PUBCHEM CID5746)
PHOTODYNAMIC THERAPY
PORFIMER SODIUM (PUBCHEM CID136187588)
RAS ONCOGENE
RESISTANCE
TEMOPORFIN (PUBCHEM CID60751)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/228158
Acceder
id CONICETDig_933750b08bf78fd6b958415bfeb2936d
oai_identifier_str oai:ri.conicet.gov.ar:11336/228158
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesionRodriguez, Lorena GabrielaDi Venosa, Gabriela MarianaRivas, Martín A.Juarranz, AngelesSanz Rodriguez, FranciscoCasas, Adriana GabrielaACRIDINE ORANGE (PUBCHEM CID62344)ADHESIONCHLORIN E6 (PUBCHEM CID5479494)CISPLATIN (PUBCHEM CID5702198)CYTOSKELETONDOXORUBICIN (PUBCHEM CID31703)FLUOROURACIL (PUBCHEM CID3385)MEROCYANINE 540 (PUBCHEM CID5702743)METHOTREXATE (PUBCHEM CID126941)MITOMYCIN C (PUBCHEM CID5746)PHOTODYNAMIC THERAPYPORFIMER SODIUM (PUBCHEM CID136187588)RAS ONCOGENERESISTANCETEMOPORFIN (PUBCHEM CID60751)https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aims: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methods: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findings: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. Significance: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.Fil: Rodriguez, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Rivas, Martín A.. Weill Cornell Medicine; Estados UnidosFil: Juarranz, Angeles. Universidad Autónoma de Madrid; EspañaFil: Sanz Rodriguez, Francisco. Universidad Autónoma de Madrid; EspañaFil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaPergamon-Elsevier Science Ltd2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228158Rodriguez, Lorena Gabriela; Di Venosa, Gabriela Mariana; Rivas, Martín A.; Juarranz, Angeles; Sanz Rodriguez, Francisco; et al.; Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion; Pergamon-Elsevier Science Ltd; Life Sciences; 314; 121287; 2-2023; 1-100024-3205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2022.121287info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0024320522009870info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:25:07Zoai:ri.conicet.gov.ar:11336/228158instacron: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 10:25:08.017CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
title Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
spellingShingle Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
Rodriguez, Lorena Gabriela
ACRIDINE ORANGE (PUBCHEM CID62344)
ADHESION
CHLORIN E6 (PUBCHEM CID5479494)
CISPLATIN (PUBCHEM CID5702198)
CYTOSKELETON
DOXORUBICIN (PUBCHEM CID31703)
FLUOROURACIL (PUBCHEM CID3385)
MEROCYANINE 540 (PUBCHEM CID5702743)
METHOTREXATE (PUBCHEM CID126941)
MITOMYCIN C (PUBCHEM CID5746)
PHOTODYNAMIC THERAPY
PORFIMER SODIUM (PUBCHEM CID136187588)
RAS ONCOGENE
RESISTANCE
TEMOPORFIN (PUBCHEM CID60751)
title_short Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
title_full Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
title_fullStr Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
title_full_unstemmed Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
title_sort Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion
dc.creator.none.fl_str_mv Rodriguez, Lorena Gabriela
Di Venosa, Gabriela Mariana
Rivas, Martín A.
Juarranz, Angeles
Sanz Rodriguez, Francisco
Casas, Adriana Gabriela
author Rodriguez, Lorena Gabriela
author_facet Rodriguez, Lorena Gabriela
Di Venosa, Gabriela Mariana
Rivas, Martín A.
Juarranz, Angeles
Sanz Rodriguez, Francisco
Casas, Adriana Gabriela
author_role author
author2 Di Venosa, Gabriela Mariana
Rivas, Martín A.
Juarranz, Angeles
Sanz Rodriguez, Francisco
Casas, Adriana Gabriela
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ACRIDINE ORANGE (PUBCHEM CID62344)
ADHESION
CHLORIN E6 (PUBCHEM CID5479494)
CISPLATIN (PUBCHEM CID5702198)
CYTOSKELETON
DOXORUBICIN (PUBCHEM CID31703)
FLUOROURACIL (PUBCHEM CID3385)
MEROCYANINE 540 (PUBCHEM CID5702743)
METHOTREXATE (PUBCHEM CID126941)
MITOMYCIN C (PUBCHEM CID5746)
PHOTODYNAMIC THERAPY
PORFIMER SODIUM (PUBCHEM CID136187588)
RAS ONCOGENE
RESISTANCE
TEMOPORFIN (PUBCHEM CID60751)
topic ACRIDINE ORANGE (PUBCHEM CID62344)
ADHESION
CHLORIN E6 (PUBCHEM CID5479494)
CISPLATIN (PUBCHEM CID5702198)
CYTOSKELETON
DOXORUBICIN (PUBCHEM CID31703)
FLUOROURACIL (PUBCHEM CID3385)
MEROCYANINE 540 (PUBCHEM CID5702743)
METHOTREXATE (PUBCHEM CID126941)
MITOMYCIN C (PUBCHEM CID5746)
PHOTODYNAMIC THERAPY
PORFIMER SODIUM (PUBCHEM CID136187588)
RAS ONCOGENE
RESISTANCE
TEMOPORFIN (PUBCHEM CID60751)
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Aims: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methods: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findings: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. Significance: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.
Fil: Rodriguez, Lorena Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
Fil: Di Venosa, Gabriela Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
Fil: Rivas, Martín A.. Weill Cornell Medicine; Estados Unidos
Fil: Juarranz, Angeles. Universidad Autónoma de Madrid; España
Fil: Sanz Rodriguez, Francisco. Universidad Autónoma de Madrid; España
Fil: Casas, Adriana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina
description Aims: Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methods: We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findings: We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. Significance: Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.
publishDate 2023
dc.date.none.fl_str_mv 2023-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/228158
Rodriguez, Lorena Gabriela; Di Venosa, Gabriela Mariana; Rivas, Martín A.; Juarranz, Angeles; Sanz Rodriguez, Francisco; et al.; Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion; Pergamon-Elsevier Science Ltd; Life Sciences; 314; 121287; 2-2023; 1-10
0024-3205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228158
identifier_str_mv Rodriguez, Lorena Gabriela; Di Venosa, Gabriela Mariana; Rivas, Martín A.; Juarranz, Angeles; Sanz Rodriguez, Francisco; et al.; Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion; Pergamon-Elsevier Science Ltd; Life Sciences; 314; 121287; 2-2023; 1-10
0024-3205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2022.121287
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0024320522009870
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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