Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis

Autores
Sukowati, Caecilia H. C.; Anfuso, Beatrice; Fiore, Esteban Juan; Ie, Susan I.; Raseni, Alan; Vascotto, Fulvia; Avellini, Claudio; Mazzolini Rizzo, Guillermo Daniel; Tiribelli, Claudio
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.
Fil: Sukowati, Caecilia H. C.. Università di Udine; Italia
Fil: Anfuso, Beatrice. No especifíca;
Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Ie, Susan I.. Eijkman Institute For Molecular Biology; Indonesia
Fil: Raseni, Alan. Institute for Research and Health Care Burlo Garofolo; Italia
Fil: Vascotto, Fulvia. Institute for Research and Health Care Burlo Garofolo; Italia
Fil: Avellini, Claudio. University Hospital Santa Maria della Misericordia; Italia
Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tiribelli, Claudio. No especifíca;
Materia
HCC
Cancer Stem Cells
Hyaluronic acid
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/149548
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/149548
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesisSukowati, Caecilia H. C.Anfuso, BeatriceFiore, Esteban JuanIe, Susan I.Raseni, AlanVascotto, FulviaAvellini, ClaudioMazzolini Rizzo, Guillermo DanielTiribelli, ClaudioHCCCancer Stem CellsHyaluronic acidhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.Fil: Sukowati, Caecilia H. C.. Università di Udine; ItaliaFil: Anfuso, Beatrice. No especifíca;Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Ie, Susan I.. Eijkman Institute For Molecular Biology; IndonesiaFil: Raseni, Alan. Institute for Research and Health Care Burlo Garofolo; ItaliaFil: Vascotto, Fulvia. Institute for Research and Health Care Burlo Garofolo; ItaliaFil: Avellini, Claudio. University Hospital Santa Maria della Misericordia; ItaliaFil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tiribelli, Claudio. No especifíca;Nature2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/149548Sukowati, Caecilia H. C.; Anfuso, Beatrice; Fiore, Esteban Juan; Ie, Susan I.; Raseni, Alan; et al.; Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis; Nature; Scientific Reports; 9; 1; 3-2019; 1-112045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-40436-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:06:12Zoai:ri.conicet.gov.ar:11336/149548instacron: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 10:06:12.376CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
title Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
spellingShingle Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
Sukowati, Caecilia H. C.
HCC
Cancer Stem Cells
Hyaluronic acid
title_short Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
title_full Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
title_fullStr Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
title_full_unstemmed Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
title_sort Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis
dc.creator.none.fl_str_mv Sukowati, Caecilia H. C.
Anfuso, Beatrice
Fiore, Esteban Juan
Ie, Susan I.
Raseni, Alan
Vascotto, Fulvia
Avellini, Claudio
Mazzolini Rizzo, Guillermo Daniel
Tiribelli, Claudio
author Sukowati, Caecilia H. C.
author_facet Sukowati, Caecilia H. C.
Anfuso, Beatrice
Fiore, Esteban Juan
Ie, Susan I.
Raseni, Alan
Vascotto, Fulvia
Avellini, Claudio
Mazzolini Rizzo, Guillermo Daniel
Tiribelli, Claudio
author_role author
author2 Anfuso, Beatrice
Fiore, Esteban Juan
Ie, Susan I.
Raseni, Alan
Vascotto, Fulvia
Avellini, Claudio
Mazzolini Rizzo, Guillermo Daniel
Tiribelli, Claudio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HCC
Cancer Stem Cells
Hyaluronic acid
topic HCC
Cancer Stem Cells
Hyaluronic acid
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.
Fil: Sukowati, Caecilia H. C.. Università di Udine; Italia
Fil: Anfuso, Beatrice. No especifíca;
Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Ie, Susan I.. Eijkman Institute For Molecular Biology; Indonesia
Fil: Raseni, Alan. Institute for Research and Health Care Burlo Garofolo; Italia
Fil: Vascotto, Fulvia. Institute for Research and Health Care Burlo Garofolo; Italia
Fil: Avellini, Claudio. University Hospital Santa Maria della Misericordia; Italia
Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tiribelli, Claudio. No especifíca;
description Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo, in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo, in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
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/11336/149548
Sukowati, Caecilia H. C.; Anfuso, Beatrice; Fiore, Esteban Juan; Ie, Susan I.; Raseni, Alan; et al.; Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis; Nature; Scientific Reports; 9; 1; 3-2019; 1-11
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/149548
identifier_str_mv Sukowati, Caecilia H. C.; Anfuso, Beatrice; Fiore, Esteban Juan; Ie, Susan I.; Raseni, Alan; et al.; Hyaluronic acid inhibition by 4-methylumbelliferone reduces the expression of cancer stem cells markers during hepatocarcinogenesis; Nature; Scientific Reports; 9; 1; 3-2019; 1-11
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-019-40436-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
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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