20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor G...

Autores
Cárdenas, Sofía; Colombero, Cecilia; Panelo, Laura Carolina; Dakarapu, Rambabu; Falck, John; Costas, Monica Alejandra; Nowicki, Susana
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
20-Hydroxyeicosatetraenoic acid (20- HETE), the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to assess in vitro if 20-HETE/GPR75 modify the metastatic features of PC-3 cells. Cells were incubated with 20-HETE or its stable analog 5,14- HEDGE (both 0.1 nM) in the presence or absence of two different antagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or 10 uM). The following assays were performed: e-cadherin and vimentin protein expression (epithelial-mesenchymal transition), zymography (release of matrix metalloproteinase-2 (MMP-2)), immunofluorescence and p-FAK (changes of cytoskeleton), scratch wound healing (migration), and soft agar colony formation (anchorage-independent growth). Results were analyzed using one-way ANOVA followed by Dunnet’s. 20-HETE (24 h) increased by 150 % the expression of vimentin (p<0.0001, n= 3) and diminished by 40 % the expression of ecadherin (p<0.0001, n= 3), whereas these effects were reversed by AAA (p<0.0001 and p<0.05, respectively). 20-HETE increased by 52 % the release of MMP-2 (p<0.05, n= 3), and this was also inhibited by AAA (p<0.001). AAA disorganized the actin filaments throughout PC-3 cells, while tubulin filaments remained unchanged. Also, 20-HETE increased by 89 % FAK phosphorylation (Y397) (p<0.0001, n= 3). 20-HETE increased by 147 % cell migration rate (p<0.0001, n= 3) and this effect was reverted by both antagonists, AAA or 19-HEDE (p<0.05 and p<0.0001, respectively), or by knockdown of GPR75 (p<0.0001). Finally, 5,14-HEDGE (21 days) formed twice the number of colonies vs. control (p<0.05, n= 2) and this was abolished by AAA (p<0.05). These results strongly suggest a role for GPR75 in 20-HETE-mediated metastatic features in PC-3 cells.
Fil: Cárdenas, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Colombero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Dakarapu, Rambabu. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Falck, John. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Reunión Anual de las Sociedades de Biociencia
Mar Del Plata
Argentina
Sociedad Argentina de Investigación Clinica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Sociedad Argentina de Protozoología
Materia
20-HETE
GPR75
PROSTATE
CANCER
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:11336/163925
Acceder
id CONICETDig_21fd5927329a6842f14aeb2efd5fb8b2
oai_identifier_str oai:ri.conicet.gov.ar:11336/163925
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75Cárdenas, SofíaColombero, CeciliaPanelo, Laura CarolinaDakarapu, RambabuFalck, JohnCostas, Monica AlejandraNowicki, Susana20-HETEGPR75PROSTATECANCERhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/320-Hydroxyeicosatetraenoic acid (20- HETE), the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to assess in vitro if 20-HETE/GPR75 modify the metastatic features of PC-3 cells. Cells were incubated with 20-HETE or its stable analog 5,14- HEDGE (both 0.1 nM) in the presence or absence of two different antagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or 10 uM). The following assays were performed: e-cadherin and vimentin protein expression (epithelial-mesenchymal transition), zymography (release of matrix metalloproteinase-2 (MMP-2)), immunofluorescence and p-FAK (changes of cytoskeleton), scratch wound healing (migration), and soft agar colony formation (anchorage-independent growth). Results were analyzed using one-way ANOVA followed by Dunnet’s. 20-HETE (24 h) increased by 150 % the expression of vimentin (p<0.0001, n= 3) and diminished by 40 % the expression of ecadherin (p<0.0001, n= 3), whereas these effects were reversed by AAA (p<0.0001 and p<0.05, respectively). 20-HETE increased by 52 % the release of MMP-2 (p<0.05, n= 3), and this was also inhibited by AAA (p<0.001). AAA disorganized the actin filaments throughout PC-3 cells, while tubulin filaments remained unchanged. Also, 20-HETE increased by 89 % FAK phosphorylation (Y397) (p<0.0001, n= 3). 20-HETE increased by 147 % cell migration rate (p<0.0001, n= 3) and this effect was reverted by both antagonists, AAA or 19-HEDE (p<0.05 and p<0.0001, respectively), or by knockdown of GPR75 (p<0.0001). Finally, 5,14-HEDGE (21 days) formed twice the number of colonies vs. control (p<0.05, n= 2) and this was abolished by AAA (p<0.05). These results strongly suggest a role for GPR75 in 20-HETE-mediated metastatic features in PC-3 cells.Fil: Cárdenas, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Colombero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Dakarapu, Rambabu. University of Texas. Southwestern Medical Center; Estados UnidosFil: Falck, John. University of Texas. Southwestern Medical Center; Estados UnidosFil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaReunión Anual de las Sociedades de BiocienciaMar Del PlataArgentinaSociedad Argentina de Investigación ClinicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioSociedad Argentina de ProtozoologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16392520-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75; Reunión Anual de las Sociedades de Biociencia; Mar Del Plata; Argentina; 2019; 80-810025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:32Zoai:ri.conicet.gov.ar:11336/163925instacron: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:34982025-09-03 09:44:32.616CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
title 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
spellingShingle 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
Cárdenas, Sofía
20-HETE
GPR75
PROSTATE
CANCER
title_short 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
title_full 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
title_fullStr 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
title_full_unstemmed 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
title_sort 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75
dc.creator.none.fl_str_mv Cárdenas, Sofía
Colombero, Cecilia
Panelo, Laura Carolina
Dakarapu, Rambabu
Falck, John
Costas, Monica Alejandra
Nowicki, Susana
author Cárdenas, Sofía
author_facet Cárdenas, Sofía
Colombero, Cecilia
Panelo, Laura Carolina
Dakarapu, Rambabu
Falck, John
Costas, Monica Alejandra
Nowicki, Susana
author_role author
author2 Colombero, Cecilia
Panelo, Laura Carolina
Dakarapu, Rambabu
Falck, John
Costas, Monica Alejandra
Nowicki, Susana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv 20-HETE
GPR75
PROSTATE
CANCER
topic 20-HETE
GPR75
PROSTATE
CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 20-Hydroxyeicosatetraenoic acid (20- HETE), the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to assess in vitro if 20-HETE/GPR75 modify the metastatic features of PC-3 cells. Cells were incubated with 20-HETE or its stable analog 5,14- HEDGE (both 0.1 nM) in the presence or absence of two different antagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or 10 uM). The following assays were performed: e-cadherin and vimentin protein expression (epithelial-mesenchymal transition), zymography (release of matrix metalloproteinase-2 (MMP-2)), immunofluorescence and p-FAK (changes of cytoskeleton), scratch wound healing (migration), and soft agar colony formation (anchorage-independent growth). Results were analyzed using one-way ANOVA followed by Dunnet’s. 20-HETE (24 h) increased by 150 % the expression of vimentin (p<0.0001, n= 3) and diminished by 40 % the expression of ecadherin (p<0.0001, n= 3), whereas these effects were reversed by AAA (p<0.0001 and p<0.05, respectively). 20-HETE increased by 52 % the release of MMP-2 (p<0.05, n= 3), and this was also inhibited by AAA (p<0.001). AAA disorganized the actin filaments throughout PC-3 cells, while tubulin filaments remained unchanged. Also, 20-HETE increased by 89 % FAK phosphorylation (Y397) (p<0.0001, n= 3). 20-HETE increased by 147 % cell migration rate (p<0.0001, n= 3) and this effect was reverted by both antagonists, AAA or 19-HEDE (p<0.05 and p<0.0001, respectively), or by knockdown of GPR75 (p<0.0001). Finally, 5,14-HEDGE (21 days) formed twice the number of colonies vs. control (p<0.05, n= 2) and this was abolished by AAA (p<0.05). These results strongly suggest a role for GPR75 in 20-HETE-mediated metastatic features in PC-3 cells.
Fil: Cárdenas, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Colombero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Dakarapu, Rambabu. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Falck, John. University of Texas. Southwestern Medical Center; Estados Unidos
Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Nowicki, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Reunión Anual de las Sociedades de Biociencia
Mar Del Plata
Argentina
Sociedad Argentina de Investigación Clinica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Sociedad Argentina de Protozoología
description 20-Hydroxyeicosatetraenoic acid (20- HETE), the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to assess in vitro if 20-HETE/GPR75 modify the metastatic features of PC-3 cells. Cells were incubated with 20-HETE or its stable analog 5,14- HEDGE (both 0.1 nM) in the presence or absence of two different antagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or 10 uM). The following assays were performed: e-cadherin and vimentin protein expression (epithelial-mesenchymal transition), zymography (release of matrix metalloproteinase-2 (MMP-2)), immunofluorescence and p-FAK (changes of cytoskeleton), scratch wound healing (migration), and soft agar colony formation (anchorage-independent growth). Results were analyzed using one-way ANOVA followed by Dunnet’s. 20-HETE (24 h) increased by 150 % the expression of vimentin (p<0.0001, n= 3) and diminished by 40 % the expression of ecadherin (p<0.0001, n= 3), whereas these effects were reversed by AAA (p<0.0001 and p<0.05, respectively). 20-HETE increased by 52 % the release of MMP-2 (p<0.05, n= 3), and this was also inhibited by AAA (p<0.001). AAA disorganized the actin filaments throughout PC-3 cells, while tubulin filaments remained unchanged. Also, 20-HETE increased by 89 % FAK phosphorylation (Y397) (p<0.0001, n= 3). 20-HETE increased by 147 % cell migration rate (p<0.0001, n= 3) and this effect was reverted by both antagonists, AAA or 19-HEDE (p<0.05 and p<0.0001, respectively), or by knockdown of GPR75 (p<0.0001). Finally, 5,14-HEDGE (21 days) formed twice the number of colonies vs. control (p<0.05, n= 2) and this was abolished by AAA (p<0.05). These results strongly suggest a role for GPR75 in 20-HETE-mediated metastatic features in PC-3 cells.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
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/11336/163925
20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75; Reunión Anual de las Sociedades de Biociencia; Mar Del Plata; Argentina; 2019; 80-81
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/163925
identifier_str_mv 20-Hydroxyeicosatetraenoic acid (20- hete) promotes a malignant phenotype in human castration-resistant prostatecancer cells through stimulation of the g protein-coupled receptor GPR75; Reunión Anual de las Sociedades de Biociencia; Mar Del Plata; Argentina; 2019; 80-81
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2010-a-2019/
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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.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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