Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/7614 |
Resumo: | Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERβ expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERβ was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17β-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis. |
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Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferationAnti-EstrogensBladder CancerEstradiol-Like MetabolitesEstrogen ReceptorsUGS-Related Bladder CancerUrogenital SchistosomiasisInfecções Sistémicas e ZoonosesEstrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERβ expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERβ was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17β-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis.Highlights: Estrogen receptor (ERs) are expressed in both urogenital schistosomiasis and bladder cancer; ERα was associated with aggressive tumor features and presence of schistosome eggs; In silico analysis shows an agonistic putative action of S. haematobium-derived metabolites for ERα; ERα induced proliferation in bladder cancer cells can be reverted by anti-estrogens; Evidence suggests that activation of ERα could play a role in urogenital schistosomiasis and urogenital schistosomiasis-induced carcinogenesis.PJB acknowledges support from award R01CA164719 from the National Cancer Institute (NCI), National Institutes of Health (NIH), USA.Elsevier/ Society of Urologic OncologyRepositório Científico do Instituto Nacional de SaúdeBernardo, CarinaSantos, JúlioCosta, CéuTavares, AnaAmaro, TeresinaMarques, IgorGouveia, Maria JoãoFélix, VítorAfreixo, VeraBrindley, Paul J.Costa, José ManuelAmado, FranciscoHelguero, LuisaSantos, Lúcio L.2021-03-31T16:02:06Z2020-092020-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7614engUrol Oncol. 2020 Sep;38(9):738.e23-738.e35. doi: 10.1016/j.urolonc.2020.04.022. Epub 2020 Jun 2.1078-143910.1016/j.urolonc.2020.04.022info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:06Zoai:repositorio.insa.pt:10400.18/7614Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:14.629627Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
title |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
spellingShingle |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation Bernardo, Carina Anti-Estrogens Bladder Cancer Estradiol-Like Metabolites Estrogen Receptors UGS-Related Bladder Cancer Urogenital Schistosomiasis Infecções Sistémicas e Zoonoses |
title_short |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
title_full |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
title_fullStr |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
title_full_unstemmed |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
title_sort |
Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation |
author |
Bernardo, Carina |
author_facet |
Bernardo, Carina Santos, Júlio Costa, Céu Tavares, Ana Amaro, Teresina Marques, Igor Gouveia, Maria João Félix, Vítor Afreixo, Vera Brindley, Paul J. Costa, José Manuel Amado, Francisco Helguero, Luisa Santos, Lúcio L. |
author_role |
author |
author2 |
Santos, Júlio Costa, Céu Tavares, Ana Amaro, Teresina Marques, Igor Gouveia, Maria João Félix, Vítor Afreixo, Vera Brindley, Paul J. Costa, José Manuel Amado, Francisco Helguero, Luisa Santos, Lúcio L. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Bernardo, Carina Santos, Júlio Costa, Céu Tavares, Ana Amaro, Teresina Marques, Igor Gouveia, Maria João Félix, Vítor Afreixo, Vera Brindley, Paul J. Costa, José Manuel Amado, Francisco Helguero, Luisa Santos, Lúcio L. |
dc.subject.por.fl_str_mv |
Anti-Estrogens Bladder Cancer Estradiol-Like Metabolites Estrogen Receptors UGS-Related Bladder Cancer Urogenital Schistosomiasis Infecções Sistémicas e Zoonoses |
topic |
Anti-Estrogens Bladder Cancer Estradiol-Like Metabolites Estrogen Receptors UGS-Related Bladder Cancer Urogenital Schistosomiasis Infecções Sistémicas e Zoonoses |
description |
Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERβ expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERβ was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17β-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-09 2020-09-01T00:00:00Z 2021-03-31T16:02:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/7614 |
url |
http://hdl.handle.net/10400.18/7614 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Urol Oncol. 2020 Sep;38(9):738.e23-738.e35. doi: 10.1016/j.urolonc.2020.04.022. Epub 2020 Jun 2. 1078-1439 10.1016/j.urolonc.2020.04.022 |
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info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier/ Society of Urologic Oncology |
publisher.none.fl_str_mv |
Elsevier/ Society of Urologic Oncology |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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