Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma

Autores
Molejon, Maria Ines; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; Soubeyran, Philippe; Iovanna, Juan Lucio
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play an important role in sensitizing PDAC to anticancer treatments since its inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this work clearly shows a heterogeneity in the effect of Chloroquine and highlights a role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that the role of autophagy is more complex than expected in PDAC as well as its sensitivity to treatments.
Fil: Molejon, Maria Ines. Institut National de la Santé et de la Recherche Médicale; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Swayden, Mirna. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Fanale, Daniele. 3 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy.; Argentina. University of Palermo. Department of Surgical, Oncological and Oral Sciences; Italia
Fil: Bintz, Jennifer. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Gayet, Odile. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Soubeyran, Philippe. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Iovanna, Juan Lucio. Institut National de la Santé et de la Recherche Médicale; Francia
Materia
AUTOPHAGY
CHLOROQUINE
GEMCITABINE
PANCREAS 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:11336/97633
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/97633
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinomaMolejon, Maria InesSwayden, MirnaFanale, DanieleBintz, JenniferGayet, OdileSoubeyran, PhilippeIovanna, Juan LucioAUTOPHAGYCHLOROQUINEGEMCITABINEPANCREAS CANCERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play an important role in sensitizing PDAC to anticancer treatments since its inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this work clearly shows a heterogeneity in the effect of Chloroquine and highlights a role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that the role of autophagy is more complex than expected in PDAC as well as its sensitivity to treatments.Fil: Molejon, Maria Ines. Institut National de la Santé et de la Recherche Médicale; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: Swayden, Mirna. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Fanale, Daniele. 3 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy.; Argentina. University of Palermo. Department of Surgical, Oncological and Oral Sciences; ItaliaFil: Bintz, Jennifer. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Gayet, Odile. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Soubeyran, Philippe. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Iovanna, Juan Lucio. Institut National de la Santé et de la Recherche Médicale; FranciaImpact Journals2018-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/97633Molejon, Maria Ines; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; et al.; Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma; Impact Journals; Oncotarget; 9; 56; 7-2018; 30837-308461949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.25745info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25745&path[]=80543info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:28:19Zoai:ri.conicet.gov.ar:11336/97633instacron: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 10:28:19.576CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
title Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
spellingShingle Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
Molejon, Maria Ines
AUTOPHAGY
CHLOROQUINE
GEMCITABINE
PANCREAS CANCER
title_short Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
title_full Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
title_fullStr Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
title_full_unstemmed Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
title_sort Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma
dc.creator.none.fl_str_mv Molejon, Maria Ines
Swayden, Mirna
Fanale, Daniele
Bintz, Jennifer
Gayet, Odile
Soubeyran, Philippe
Iovanna, Juan Lucio
author Molejon, Maria Ines
author_facet Molejon, Maria Ines
Swayden, Mirna
Fanale, Daniele
Bintz, Jennifer
Gayet, Odile
Soubeyran, Philippe
Iovanna, Juan Lucio
author_role author
author2 Swayden, Mirna
Fanale, Daniele
Bintz, Jennifer
Gayet, Odile
Soubeyran, Philippe
Iovanna, Juan Lucio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOPHAGY
CHLOROQUINE
GEMCITABINE
PANCREAS CANCER
topic AUTOPHAGY
CHLOROQUINE
GEMCITABINE
PANCREAS CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play an important role in sensitizing PDAC to anticancer treatments since its inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this work clearly shows a heterogeneity in the effect of Chloroquine and highlights a role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that the role of autophagy is more complex than expected in PDAC as well as its sensitivity to treatments.
Fil: Molejon, Maria Ines. Institut National de la Santé et de la Recherche Médicale; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina
Fil: Swayden, Mirna. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Fanale, Daniele. 3 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy.; Argentina. University of Palermo. Department of Surgical, Oncological and Oral Sciences; Italia
Fil: Bintz, Jennifer. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Gayet, Odile. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Soubeyran, Philippe. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Iovanna, Juan Lucio. Institut National de la Santé et de la Recherche Médicale; Francia
description In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play an important role in sensitizing PDAC to anticancer treatments since its inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this work clearly shows a heterogeneity in the effect of Chloroquine and highlights a role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that the role of autophagy is more complex than expected in PDAC as well as its sensitivity to treatments.
publishDate 2018
dc.date.none.fl_str_mv 2018-07
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/11336/97633
Molejon, Maria Ines; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; et al.; Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma; Impact Journals; Oncotarget; 9; 56; 7-2018; 30837-30846
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/97633
identifier_str_mv Molejon, Maria Ines; Swayden, Mirna; Fanale, Daniele; Bintz, Jennifer; Gayet, Odile; et al.; Chloroquine plays a cell-dependent role in the response to treatment of pancreatic adenocarcinoma; Impact Journals; Oncotarget; 9; 56; 7-2018; 30837-30846
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.25745
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25745&path[]=80543
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
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
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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